Purine analog nucleoside and nucleotide compounds

ABSTRACT

The invention concerns nucleoside derivatives of the formula I ##STR1## in which Ba signifies an indolyl (A), benzimidazolyl (B), pyrrolopyridinyl (C), imidazopyridinyl (D), triazolopyrimidinyl (E), imidazotriazinyl (F) or imidazopyrimidinyl (G) group substituted by R 1 , R 2  and R 3 , in which R 1 , R 2  and R 3 , which can be the same or different, signify hydrogen, halogen, a C 1  -C 7  -alkyl, C 2  -C 7  -alkenyl, hydroxy, mercapto, C 1  -C 7  -alkylthio, C 1  -C 7  -alkoxy, C 2  -C 7  -alkenyloxy, ar-C 1  -C 5  -alkyl, ar-C 2  -C 5  -alkenyl, ar-C 1  -C 5  -alkoxy, ar-C 2  -C 5  -alkenyloxy, aryloxy, nitro, amino-C 1  -C 7  -alkyl, C 1  -C 7  -alkylamino-C 1  -C 7  -alkyl, di-C 1  -C 7  -alkylamino-C 1  -C 7  -alkyl, amino, a substituted amino group --NMR 4  or --N(R 4 ) 2  or an imino group --N═CH--R 4 , and R 4  has the meaning given in the description, R 5 , R 6 , R 7  and R 8  each signify hydrogen or one or two of the radicals R 5 , R 6 , R 7  and R 8  a hydroxyl, halogen, cyano, azido or a substituted amino group --NHR 4  or --N(R 4 ) 2  or R 5  and R 7  can together represent a further bond between C-2&#39; and C-3&#39; and Y represents hydrogen or a C 1  -C 7  -alkylcarbonyl, monophosphate, diphosphate or triphosphate group, whereby &#34;aryl&#34; signifies a phenyl or naphthyl group and &#34;hetaryl&#34; a furanyl, thienyl or pyridyl group, as well as their possible anomers, N 7  - or N 9  -regioisomers (purine nomenclature), tautomers and salts.

The invention concerns nucleoside and nucleotide derivatives, processesfor the preparation of these compounds, as well as their use in thesequencing of nucleic acids.

The subject of the present invention are new nucleoside and nucleotidederivatives of the general formula I ##STR2## in which Ba signifies anindolyl (A), benzimidazolyl (B), pyrrolopyridinyl (C), imidazopyridinyl(D), triazolopyrimidinyl (E), imidazotriazinyl (F) or imidazopyrimidinyl(G) radical, ##STR3## whereby R¹, R², R³, which can be the same ordifferent, signify hydrogen, halogen, a C₁ -C₇ -alkyl, C₂ -C₇ -alkenyl,hydroxyl, mercapto, C₁ -C₇ -alkylthio, C₁ -C₇ -alkoxy, C₂ -C₇-alkenyloxy, ar-C₁ -C₅ -alkyl, ar-C₂ -C₅ -alkenyl, ar-C₁ -C₅ -alkoxy,ar-C₂ -C₅ -alkenyloxy, aryloxy, nitro, amino-C₁ -C₇ -alkyl, C₁ -C₇-alkylamino-C₁ -C₇ -alkyl, di-C.sub. -C₇ -alkylamino-C₁ -C₇ -alkyl,amino, a substituted amino group --NHR⁴ or --N(R⁴)₂ or an imino group--N═CH--R⁴, whereby R⁴ can signify a C₁ -C₇ -alkyl, C₂ -C₇ -alkenyl, C₃-C₇ -cycloalkyl, C₃ -C₇ -cycloalkyl-C₁ -C₇ -alkyl, C₃ -C₇ -cycloalkenyl,C₁ -C₇ -alkoxy-C₁ -C₇ -alkyl, halogen-C₁ -C₇ -alkyl-, hydroxy-C₁ -C₇-alkyl-, ar-C.sub. 1 -C₅ -alkyl, ar-C₂ -C₅ -alkenyl, hetaryl-C₁ -C₅-alkyl or hetaryl-C₂ -C₅ -alkenyl group, whereby the aryl and hetarylmoieties can be substituted one, two or three times by C₁ -C₆ -alkyl, C₂-C₆ -alkenyl, C₁ -C₆ -alkoxy, halogen or hydroxyl, or R⁴ can signify anamino-C₁ -C₇ -alkyl, C₁ -C₇ -alkylamino-C₁ -C₇ -alkyl or di-C₁ -C₇-alkylamino-C₁ -C₇ -alkyl group and, in the case of the --NHR⁴ and--N═CH--R⁴ group, R⁴ can additionally be an mino, C₁ -C₇ -alkylamino,di-C₁ -C₇ -alkylamino or C₁ -C₇ -alkoxy group or, in the case of the--N(R⁴)₂ group, the two nitrogen substituents R⁴ together form a C₁ -C₇-alkylidene radical which, in turn, can be substituted by a C₁ -C₇-alkoxy, C₁ -C₇ -alkylamino or di-C₁ -C₇ -alkylamino group, R⁵, R⁶, R⁷and R⁸ in each case signify hydrogen or one or two of the residues R⁵,R⁶, R⁷ and R⁸ signify hydroxyl, halogen, cyano, azido or a substitutedamino group --NHR⁴ or --N(R⁴)₂ or R⁵ and R⁷ can together represent afurther bond between C-2' and C-3' and Y represents hydrogen or a C₁ -C₇-alkylcarbonyl, monophosphate, diphosphate or triphosphate group,whereby "aryl" is to signify a phenyl or naphthyl group and "hetaryl" afuranyl, thienyl or pyridyl group, with the proviso that

a) for the case that R⁶ is a hydroxyl group, R⁸ cannot be a hydrogenatom or a hydroxyl group,

b) for the case that Ba is the group (B), cannot be R⁶ cannot be ahalogen or azido group,

c) for the case that Ba is the group (D) and R² hydrogen, R¹ cannot be achlorine or amino group and R⁶ cannot be a hydrogen or chlorine atom and

d) for the case that Ba is the group (E) and R¹ the amino group, R⁵ andR⁷ cannot together form a bond;

as well as the possible α- and β-anomers thereof, N⁷ -, N⁸ - or N⁹-regioisomers (purine nomenclature), tautomers and salts, as well asnucleic acids which contain compounds of the formula I as constructionalunits.

Similar compounds of the formula I are known from EP-A-286,028. Thepresent compounds according to the invention differ structurally fromthe known compounds by the bases given in the definition of Ba.

The compounds of the general formula I are preponderantly new compounds.

From the prior art are already known a plurality of ribofuranosylderivatives (R⁶ =R⁸ =OH), as well as the corresponding2'-desoxyribofuranosyl derivatives (R⁶ =OH; R⁸ =H) which, however, arenot included by the present invention due to the disclaimer a).

Furthermore, from the literature (Bioorg. Khim., 13, 1375, 1987) areknown benzimidazoles unsubstituted in the base moiety (base type B)which contain, in the sugar moiety in the 3'-position halogen, azido andamino radicals and which, as triphosphates, have been investigated invitro with regard to their substrate specificity for DNA biosyntheses.The synthesis of the corresponding nucleosides has also been published(Z. Chem., 25, 180, 1985 and Synthesis, 410/1985). These compounds arenot included by the product claim due to the disclaimer b). Of the3-deazapurinenucleosides (purine nomenclature; base type D), thesynthesis is known of derivatives which contain chlorine or an aminogroup in the 6-position and are substituted in the ribose in the3'-position by hydrogen or a chlorine atom (Nucleic Acids Res., 15,1121, 1987 and Nucleosides Nucleotides, 3,413, 1984). These compoundsare not included by the product claim due to the disclaimer c). Apharmacological action of these compounds has not been described. InU.S. Pat. No. 3,817,982 is described an 8-aza-6-aminopurine derivative(base type E) with a 2', 3'-didehydro-2', 3'-didesoxyribose radicalwhich can find use as antibiotic, virostatic and in the case of DNAreplication studies. This compound is not included by the product andmedicament claims due to the disclaimer d).

Furthermore, from the literature are already known some compounds of theformula I in which Y signifies a hydrogen atom (nucleosides) or analkylcarbonyl group and either R⁶ and R⁸ simultaneously representhydroxyl (ribose derivatives) or R⁶ hydroxyl and R⁸ a hydrogen atom(2'-desoxyribose derivatives). These compounds are excluded from theproduct claim due to the disclaimer a). The same applies to the2'-desoxyribofuranosylnucleosides with the base type (D) known fromEP-A-0,038,569 which possess an inflammation-inhibiting action.

Furthermore, from EP-A-0,043,722 are knownβ-D-arabinofuranosylnucleosides with the base type (D) as antiviralagents. In the case of these compounds, it is a question of furanosylderivatives in which R⁵ and R⁶ each signify a hydroxyl group and R⁸ ahydrogen atom. These derivatives are not covered by the claims on thebasis of disclaimer a).

For the case that Ba represents the base type (B) or (D), then the N⁷ -and N9-regioisomers are also the subject of the present invention andfor the case that Ba represents a triazolopyrimidine group (base typeE), also the corresponding N⁷ -, N⁸ - or N⁹ -regioisomers. Theseparation of the various regioisomers takes place according to per seknown methods, such as for example by column chromatography.

The "alkyl" or "alkenyl" moieties in the definition of the substituentsR¹, R², R³ and R⁴ can be straight-chained or branched and contain 1-7,preferably 1-4 carbon atoms. The methyl and the ethyl group are quiteespecially preferred, for R⁴ also the propyl and isobutyl group.

By halogen in the definition of the substituents R¹, R², R³, R⁵, R⁶, R⁷and R⁸ are understood fluorine chlorine, bromine and iodine, especiallypreferred is the fluorine and chlorine atom.

The aralkyl, hetaralkyl and aralkoxy radicals occurring in thedefinitions of the substituents R¹, R², R³ and R⁴ preferably contain analkylene chain with 1-5 or 1-3 carbon atoms, respectively, which issubstituted once or twice with an aromatic radical, for example phenylor naphthyl radical. The aryl moieties of the previously mentionedaralkyl, aralkoxy or hetarylalkyl groups can, in turn, be substitutedone, two or three times by an alkyl, hydroxyl, halogen or alkoxy groupwith, in each case, 1-6 preferably 1-3 carbon atoms. The benzyl andhetarylmethyl group is especially preferred as aralkyl group.

As aryloxy radicals in the definition of the substituents R¹, R² and R⁴,phenyloxy radicals are especially preferred which can possibly besubstituted one, two or three times by further substituents, such as forexample nitro, alkyl and alkoxy groups, whereby the alkyl and alkoxygroups can contain 1-6 carbon atoms.

By "aryl" are to be understood the phenyl and naphthyl group. The"hetaryl" groups are preferably the furanyl, thienyl or pyridyl group.

The amino group occurring in the definition of the substituents R¹, R²,R³, R⁵, R⁶, R⁷ and R⁸, which can possibly be substituted once or twiceby R⁴, contain, as possible substituents, preferably alkyl, alkenyl,cycloalkyl, alkoxyalkyl, haloalkyl, aralkyl and dialkylaminoalkylgroups, whereby the alkyl and alkenyl moieties of the above-mentionedgroups preferably contain 1-5 or 1-3 carbon atoms, respectively.

The two nitrogen substituents R⁴ can together also represent analkylidene, preferably a methylidene radical which, in turn, can besubstituted by alkoxy or by substituted amino groups. A quite especiallypreferred substituent of this type is the dimethylaminomethylidenegroup.

The monophosphate group is the group --PO(OH)₂, the diphosphate groupthe group --P₂ O₃ (OH)₃ and the triphosphate group the group --P₃ O₅(OH)₄.

As possible salts, there come into question especially alkali metal,alkaline earth metal and ammonium salts of the phosphate groups. Asalkali metal salts, lithium, sodium and potassium salts are preferred.As alkaline earth metal salts, magnesium and calcium salts especiallycome into question. By ammonium salts, according to the invention areunderstood salts which contain the ammonium ion which can be substitutedup to four times by alkyl radicals with 1-4 carbon atoms and/or aralkylradicals, preferably benzyl radicals. The substituents can hereby be thesame or different. The salts of the phosphates can be converted in knownmanner into the free acids.

The compounds of the formula I can contain basic groups, especiallyamino groups, which can be converted with suitable acids intoacid-addition salts. As acids for this purpose, there come intoconsideration for example: hydrochloric acid, hydrobromic acid,sulphuric acid, phosphoric acid, fumaric acid, succinic acid, tartaricacid, citric acid, lactic acid, maleic acid or methane-sulphonic acid.

Especially preferred compounds of the general formula I are those whichare designated as glyceropentofuranosides, especially their didesoxy,didesoxydidehydro and didesoxy-3'-fluoro derivatives. In this sense, thefollowing meanings of R⁵ -R⁸ come into question: R⁵ preferablyrepresents a hydrogen atom or a fluorine atom, R⁷ a hydrogen atom or ahydroxyl group or R⁵ and R⁷ together form a bond. R⁶ and R⁸ especiallysignify a hydrogen atom or a fluorine or azido group.

For R¹ -R³ and R⁵ -R⁸, the following groups especially come intoquestion: for R¹ hydrogen, amino, chlorine, C₁ -C₆ -alkoxy, especiallymethoxy, or nitro; for R² hydrogen or amino; for R³ hydrogen; for R⁵ -R⁸hydrogen or R⁵ and R⁷ together form a bond(2',3'-didesoxy-2',3'-didehydroribofuranosyl derivatives).

Depending upon the base type (A)-(G), for the radicals R¹ -R⁸, thefollowing groups especially come into question:

When Ba is the group (A), then R¹ preferably signifies an amino or nitrogroup and R², ³, R⁵ -R⁸ in each case a hydrogen atom or R⁵ and R⁷together also a bond.

When Ba is the group (B), then R¹ -R³ and R⁵ -R⁸ preferably signify ahydrogen atom.

When Ba is the group (C), then R¹ preferably signifies a hydrogen atomor an amino or nitro group and R², R³ and R⁵ -R⁸ each a hydrogen atom orR⁵ and R⁷ together also a bond.

When Ba is the group (D), then R¹ preferably signifies an amino orchlorine group and R², R³, R⁵ -R⁸ each a hydrogen atom.

When Ba is the group (E), then R¹ preferably signifies an amino or a C₁-C₆ -alkoxy group and R², R⁵ -R⁸ each a hydrogen atom.

When Ba is the group (F), then R² preferably signifies a hydrogen atomor an amino group and R³, R⁵ -R⁸ preferably a hydrogen atom.

When Ba is the group (G), then R² preferably signifies a hydrogen atomor an amino or chlorine group and R³, R⁵ -R⁸ a hydrogen atom

The compounds according to the invention can be prepared analogously tothe known, related compounds. For the preparation of the compounds ofthe formula I, a process has proved to be especially expedient in whichone reacts a compound of the formula II

    Ba--X                                                      (II)

in which Ba has the above-given meaning and X signifies hydrogen or analkali metal group, such as e.g. lithium or sodium, with a compound ofthe formula III ##STR4## in which R⁵, R⁶, R⁷ and R⁸ have the above-givenmeaning, R' signifies an oxygen protective group and Z a reactive group,to give a compound of the formula IV ##STR5## in which Ba, R¹, R², R³,R⁵, R⁶, R⁷, R⁸ and R' have the above-given meaning, and splits offoxygen protective groups possibly present and thereafter possiblyconverts a compound so obtained, in which R⁵, R⁶, R⁷ or R⁸ signifies ahydroxyl group, after previous selective protection of the 5'-hydroxylgroup, with a halide, cyanide or azide in known manner into a compoundof the formula I, in which R⁵, R⁶, R⁷ or R⁸ signifies halogen or a cyanoor azido group, or desoxygenates in known manner to give a compound ofthe formula I, in which R⁵, R⁶, R⁷ or R⁸ signifies hydrogen, or reducesa so obtained compound of the formula I, in which R⁵, R⁶, R⁷ or R⁸ is anazido group, in known manner to give a compound of the formula I, inwhich R⁵, R⁶, R⁷ or R⁸ is an amino group, and, if desired, subsequentlyconverts compounds of the formula I, in which Y signifies hydrogen, inknown manner into the mono-, di- or triphosphates and, if desired,converts free bases or acids obtained into the corresponding salts orsalts obtained into the corresponding free bases or acids.

The compounds of the formula II are reacted with the compounds of theformula III especially advantageously under phase transfer conditions.Under the conditions of phase transfer catalysis, the bases of theformula II are converted into a corresponding anion, for example bymeans of a 50% aqueous sodium hydroxide solution. The anion thusresulting is hydrophobed by a phase transfer catalyst, for exampletris-[2-(2-methoxyethoxy)-ethyl]-amine, and transported into the organicphase in which it reacts with the reactive compound of the formula III.

As reactive group Z in the compounds of the general formula III, therepreferably come into question halogen, acetoxy and alkoxy groups. In thecase of this reaction, the hydroxyl groups of the sugar residue areprotected in the usual way by the oxygen protective groups known to theexpert, for example toluoyl, benzoyl, tetrahydropyranyl or acetylgroups. After ending of the reaction, the oxygen protective groups canagain be split off in known manner under alkaline conditions, oneexpediently using a 1M methanolic methanolate solution.

It can be expedient also to keep the radicals R¹, R² and R³ protectedduring the reaction by means of suitable protective groups. A furtheradvantageous method for the preparation of the compounds of the formulaIV is the solid-liquid phase transfer process with the use of solid,powdered potassium hydroxide, the above-mentioned kryptands, as well asthe compounds of the formulae II and III in an aprotic solvent.

Compounds of the formula I, in which R⁵, R⁶, R⁷ or R⁸ signifies halogenor an azido group, are preferably prepared in that one starts fromcompounds of the formula I, in which R⁵, R⁶, R⁷ or R⁸ represents ahydroxyl group. The hydroxyl group in the 5'-position is firstselectively protected. For this purpose, too, known processes are alsoavailable to the expert. For example, in nucleotide chemistry, the4,4'-dimethoxytriphenylmethyl group has proved to be useful. After thereaction has taken place, this can again be easily split off by mildacid hydrolysis, whereas the also acid-labile glycosidic bond is nothydrolysed under these conditions. The reaction of the nucleoside to beprotected with the oxygen protective group reagent for the 5'-hydroxylgroup is carried out in a suitable organic solvent, expediently drypyridine, with a small excess of the oxygen protective group reagent, aswell as possibly a suitable adjuvant base, for exampleN-ethyldiisopropylamine.

The so protected compound of the formula I is reacted with a halide,expediently an alkali metal halide or an organic halide, or with anazide, expediently with an alkali metal azide, such as e.g. lithiumazide, in generally known manner. The OH group on the C-2' or C-3' atomis thereby nucleophilically substituted by the halide or azide.

Compounds of the formula I, in which R⁵, R⁶, R⁷ or R⁸ signifies ahydroxyl group, can also, after previous protection of the 5'-hydroxylgroup in the above-given manner, be desoxygenated according to knownmethods, whereby compounds of the formula I result, in which R⁵, R⁶, R⁷or R⁸ signify hydrogen. For this purpose, the compound of the generalformula I, in which R⁵, R⁶, R⁷ or R⁸ represents a hydroxyl group inwhich the 5'-hydroxyl group has been protected in the above-given mannerand also other functional groups carry protective groups, is firstconverted into a 2'- or 3'-O-thiocarbonyl derivative which issubsequently radical-reduced with tributyl tin hydride. Such methods forthe desoxygenation of 2'-desoxynucleosides to 2'- and3'-didesoxynucleosides are known to the expert. The Bartondesoxygenation method has proved to be especially suitable (J. Chem.Soc., Perkin Trans. I (1975) 1574).

Compounds of the formula I, in which R⁵ and R⁷ represent a further bondbetween C-2' and C-3', can be prepared analogously to known relatedcompounds (Robins and Hansske, Tetrahedron Letters, 25, 367, 1984, andliterature cited herein). For the preparation of these compounds, aprocess has proved to be especially expedient in which one reacts theappropriate riboses with acetoxyisobutyryl bromide and subsequentlyreduces the resulting isomers with a reducing agent, such as e.g. thezinc/copper pair or similar reducing agents, and, after splitting off ofthe protective group under alkaline conditions, obtains the 2',3'-didesoxy-2', 3'-didehydro derivative from the crude product obtained.

Besides this process, further processes are described in the literaturefor the didesoxygenation and simultaneous introduction of the doublebond (cf. Jain et al., J. Org. Chem., 39, 30, 1974; Robins et al.,J.A.C.S., 98, 8204 and 8213, 1976; Adachi et al., J. Org. Chem., 44,1404, 1979; Mengel et al., Tetrah. Lett., 4203, 1977; Classon et al.,Acta Chem. Scand., B 36,251, 1982; Chu et al., J. Org. Chem., 54, 2217,1989). Furthermore, these compounds can be prepared from thecorresponding 2'-desoxyriboses according to known processes (cf. Horwitzet al., J.A.C.S., 86, 1896, 1964; McCarthy et al., J.A.C.S., 88, 1549,1966; Samukov et al., Biorg. Khim., 9, 52, 1982) of monodesoxygenationwith the simultaneous introduction of the double bond. A further routefor the preparation of these compounds is the reaction of a 2',3'-didesoxy-2', 3'-didehydroribose with an appropriately substitutedbase derivative Ba, such as is known to an expert from the literature(cf. e.g. EP-A-0,286,028).

Compounds of the formula I, in which R⁵, R⁶, R⁷ or R⁸ signifies an aminogroup, are expediently prepared in that one reduces compounds of theformula I in which this residue R⁵, R⁶, R⁷ or R⁸ represents an azidogroup. This reduction of the azido group to the amino group can takeplace according to various generally known methods. The reduction withhydrogen on a palladium-carbon catalyst has proved to be especiallyadvantageous.

The phosphate groups are introduced in known manner into compounds ofthe general formula I, in which Y signifies hydrogen. One obtains themonophosphates, for example, in that one phosphorylates compounds of theformula I, in which Y signifies hydrogen, with phosphorus oxychloride intrimethyl phosphate. The triethylammonium salts obtained in this way canbe converted in known manner into other salts by transsalification. Thedi- and triphosphates are obtained according to known methods,preferably from the monophosphates, by reaction with o-phosphates orpyrophosphates. Their various salts can also be prepared according toknown methods.

The compounds of the formula II are known compounds or can be preparedanalogously to known compounds. Such processes of preparation aredescribed, for example in Chem. Bet., 110 (1977), 1462; J. Chem. Soc.,1960, 131 and Tetrahedron Lett., 21 (1980), 3135.

Some of the compounds of the formula III are also known compounds.Compounds which have hitherto not been described can be preparedcompletely analogously to the known compounds. The preparation of such acompound is described, for example, in Chem. Ber., 93 (1960) 2777 andSynthesis, 1984, 961.

Surprisingly, it has now been found that compounds of the formula Iinhibit the multiplication of DNA and RNA viruses at the stage of thevirus-specific DNA or RNA transcription. The substances can especiallyinfluence the multiplication of retroviruses via the inhibition of theenzyme reverse transcriptase or via a chain breakage of the growing DNAchain (cf. Proc. Natl. Acad. Sci., USA, 83, 1911, 1986 and Nature, 325,773, 1987 ).

The substances of the formula I according to the invention can also beadvantageously used in the DNA sequencing according to Sanger.Especially the sequencing of d(G-C)-rich DNA fragments is made difficultby the formation of secondary structures which lead to a bandcompression in the region of d(G-C) clusters. By means of thereplacement of 2'-desoxyguanosine triphosphate or 2'-desoxyadenosinetriphosphate by compounds according to the invention, in which R⁶represents a hydroxyl group, the band compression is largely overcome.

The compounds of the formula I according to the invention, in which R⁶and R⁷ signify hydrogen, are used in the DNA sequencing according toSanger as chain terminators instead of the known 2',3'-didesoxycompounds.

Nucleic acids which, as constructional units, contain one or morecompounds of the formula I can be prepared according to known processes(for example, Nucleic Acids Research, 14, No. 5, 1986, p. 2319 et seq.).However, they also result, for example, in the case of the DNAsequencing. If compounds of the formula I, in which R⁶ signifies ahydroxyl group, are used as constructional units, then a nucleic acidcan have several such constructional units; if, as constructional unit,a compound of the formula I is used, in which R⁶ signifies hydrogen,then such a constructional unit can only be incorporated once, namely atthe end of the chain. The nucleic acids according to the invention aremade up of 2 to 1000, preferably 8 to 50 nucleotide constructionalunits. Nucleic acids with 15-30 nucleotide constructional units areespecially preferred.

Besides the compounds mentioned in the Examples, in the meaning of thepresent invention, for example, the following compounds come intoquestion:

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-amino-1H-indole

1-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-4-amino-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-diamino-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-6-hydroxy-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-6-hydroxy-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylamino-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-dihydroxy-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-hydroxy-6-amino-1H-indole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methyl-1H-indole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-amino-6-chloro-1H-indole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-mercapto-1H-indole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methylmercapto-1H-indole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methoxy-1H-indole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-dimethylamino-1H-indole

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-4-amino-1H-indole

1-(2,3-didesoxy-2-fluoro-β-D-arabinofuranosyl)-4-amino-1H-indole

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-4-amino-1H-indole

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-diaminobenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-6-hydroxybenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-6-hydroxybenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylaminobenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-dihydroxybenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-hydroxy-6-aminobenzimidazole

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylbenzimidazole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-amino-6-chlorobenzimidazole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-mercaptobenzimidazole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methylmercaptobenzimidazole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methoxybenzimidazole

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-dimethylaminobenzimidazole

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-2-fluoro--D-arabinofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-4-aminobenzimidazole

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-4-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-diamino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-6-hydroxy-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-6-hydroxy-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylamino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-dihydroxy-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-hydroxy-6-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methyl-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-amino-6-chloro-lH-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-mercapto-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methylmercapto-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methoxy-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-dimethylamino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-4-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2-fluoro-β-D-arabinofuranosyl)-4-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-4-amino-1H-pyrrolo[2,3-b]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-diamino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-6-hydroxy-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-6-hydroxy-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylamino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-dihydroxy-1H-imidazo[4,6-c]pyridine

1-(2,3-didesoxy-βD-glyceropentofuranosyl)-4-hydroxy-6-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methyl-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-amino-6-chloro-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-mercapto-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methylmercapto-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methoxy-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-dimethylamino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2-fluoro-β-D-arabinofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-4-amino-1H-imidazo[4,5-c]pyridine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-diamino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-6-hydroxy-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-6-hydroxy-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methylamino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4,6-dihydroxy-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-hydroxy-6-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-4-methyl-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-amino-6-chloro-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-mercapto-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methylmercapto-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-methoxy-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-4-dimethylamino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2-fluoro-β-D-arabinofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-4-amino-1H-triazolo[4,5-d]pyrimidine

8-(2,3-didesoxy-β-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

8-(2,3-didesoxy-3-fluoro-β-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

8-(2,3-didesoxy-3-azido-β-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

8-(2,3-didesoxy-β-D-glyceropentofuranosyl)-2-aminoimidazo[1,2-a]-s-triazin-4-one

8-(2,3-didesoxy-β-D-glyceropentofuranosyl)-2-hydroxyimidazo[1,2-a]-s-triazin-4-one

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-2-chloro-8H-imidazo[1,2-a]-s-triazin-4-one

1-(2,3-didesoxy-2,2-difluoro-β-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

1-(2,3-didesoxy-2-fluoro-β-D-arabinofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one

1-(2,3-didesoxy-2-azido-β-D-arabinofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one.

The invention is explained in more detail by the following Examples:

EXAMPLE 11-(2,3-Didehydro-2,3-didesoxy-β-D-glyceropentofuranosyl)-4-amino-1H-indole.

a)1-[2-Desoxy-3,5-di-O-(p-toluoyl)-β-D-erythropentofuranosyl]-4-nitro-1H-indole.

To a solution of 4-nitroindole (972 mg, 6.0 mmol) in CH₃ CN (50 ml) oneadds KOH (838 mg, 15.0 mmol) and TDA-1 (100 mg, 0.31 mmol) and stirs for15 min. at RT (N₂ atmosphere). After the addition of the halogenose(2.45 g, 6.3 mmol), one further stirs for 15 min. at RT, filters,evaporates to dryness and chromatographs the residue over a shortsilicagel-60H column. Evaporation of the main zone and crystallisation frombenzene/cyclohexane (1:2) gives yellow needles (2.70 g, 85%) (82%; N.D.Girgis, H. B. Cottam and R. K. Robins, J. Heterocycl. Chem., 25, 361(1988); Rf (CH₂ Cl₂ /EtOAc 99:1)=0.6; Rf (CH₂ Cl₂)=0.4.

¹ H NMR ([D₆ ]DMSO): δ=2.37, 2.41 (2s, 6H, 2 CH₃), 2.78 (m, 1H, H-2'b),3.03 (m, 1H, H-2'a), 4.56 (m, 3H, H-4' and H-5'), 5.74 (m, 1H, H-3'),6.75 (dd, J=5.9 Hz and 7.8 Hz, 1H, H-1'), 7.13 (d, J=3.1 Hz, H-3),7.29-7.40 (m, 5H, aromat. H), 7.83-8.02 (m, 5H, aromat. H and H-6), 8.11(d, J=7.9 Hz, 1H, H-5), 8.25 (d, J=8.2 Hz, 1H, H-7).

b) 1-(2-Desoxy-β-D-erythro-pentofuranosyl)-4-nitro-1H-indole.

The compound obtained in a) (3.86 g, 7.5 mmol) is mixed with MeOH (200ml) and, together with NaOMe/MeOH solution (1M, 15.5 ml), stirred for 48h at room temperature. After the addition of silica gel 60 (50 g), oneevaporates to dryness and chromatographs on silica gel 60H (column 3×30cm, elution agent CHC₃ /MeOH 8:1, Rf=0.3). Elution of the main zonegives, after evaporation of the solvent, a yellow solid in 80% yield.(96%, N. S. Girgis, H. B. Cottam and R. K. Robins, J. Heterocycl. Chem.,25, 361 (1988)).

¹ H NMR ([D₆ ]DMSO): δ=2.31 (m, 1H, H-2'b), 2.51 (m, 1H, H-2'a), 3.55(m, 2H, H-5'), 3.87 (m, 1H, H-4'), 4.40 (m, 1H, H-3'), 4.97 (m, 1H,5'-OH), 5.36 (m, 1H, 3'-OH), 6.51 (pt, J=6.5 Hz, 1H, H-1'), 7.11 (d,J=3.2 Hz, 1H, H-3), 7.36 (t, J=8.1 Hz, 1H, H-6), 8.03 (d, J=3.2 Hz, 1H,H-2), 8.10 (d, J=8.0 Hz, 1H, H-5), 8.17 (d, J=8.2 Hz, 1H, H-7).

c) 4-Amino-1-(2-desoxy-β-D-erythro-pentofuranosyl)-1H-indole(1,3,7-tridesaza-2'-desoxyadenosine).

1.0 g of the compound obtained in b) is dissolved in 50 ml ethanol andhydrogenated in the presence of 100 mg Pd/carbon (10% Pd) for 6 h at RTand normal pressure. One filters, adsorbs on silica gel andchromatographson silica gel 60 (column 15×3.5 cm). One obtains acolourless foam (yield 70%) (74%, N. S. Girgis, H. B. Cottam and R. K.Robins, J. Heterocycl. Chem., 25, 361 (1988).

¹ H NMR ([D₆ ]DMSO): δ=2.17 (m, 1H, H-2'b), 2.42 (m, 1H, H-2'a) , 3.51(m, 2H, H-5'), 3.79 (m, 1H, H-4'), 4.32 (m, 1H, H-3'), 4.89 (m, 1H,5'-OH), 5.26 (m, NH₂ and 3'-OH), 6.23 (m, 2H, H-5 and H-1'), 6.59 (d,J=3.3 Hz, 1H, H-3), 6.71 (d, J=8.2 Hz, 1H, H-7), 6.84 (pt, J=8.2 Hz, 1H,H-6), 7.31 (d, J=3.3 Hz, 1H, H-2).

4-{[(Dimethylamino)-methylene]-amino}-1-(2-desoxy-β-D-erythro-pentofuranosyl)-1H-indole.

1.54 g (6.21 mmol) of the compound obtained in c) are dissolved in 30 mldry, amine-free dimethylformamide and mixed with 12 ml (68.3 mmol)N,N-dimethylformamide diethylacetal. The reaction mixture is stirred for8h at 50° C. under argon. The solvent is evaporated off in a vacuum andthe residue subsequently evaporated several times with toluene.Chromatography on silica gel 60 H (column 13×5 cm, elution agent CHCl₃/MeOH 5:1) gives 1.28 g (68%) of colourless, foamy product; TLC(CHCl₃/MeOH 5:1): Rf=0.4.

¹ H NMR ([D₆ ]DMSO): δ=2.19 (m, 1H, H-2'b), 2.46 (m, 1H, H-2'a), 3.01(s, 6H, 2 CH₃), 3.51 (m, 2H, H-5'2), 3.81 (m, 1H, H-4'),4.34 (m, 1H,H-3'), 4.89 (m, 1H, 5'-OH), 5.29 (d, J=4.2 Hz, 1H, 3'-OH), 6.31 (dd,J=6.2 and 7.6 Hz, 1H, H-1'), 7.00 (t, J=7.8 Hz, 1H, H-6), 7.13 (d, J=7.8Hz, 1H, H-), 7.43 (d, J=3.4 Hz, 1H, H-2), 7.80 (s, 1H, CH).

e)4-{[(Diemthylamino)-methylene]-amino}-1-[2-desoxy-5-O-(tert.-butyl-diphenylsilyl)-β-D-erythropentofuranosyl]-1H-indole.

1.6 g (5.27 mmol) of the compound obtained in d) are evaporated ×2 withpyridine and subsequently dissolved in pyridine (26 ml). TBDPSiCl (1.63ml, 6.36 mmol) is added dropwise in the cold and the solution stirredfor 30 min at 0° C. One allows to warm to RT and stirs for a further 24h. The solvent is evaporated off and the residue subsequently evaporatedwith toluene. UV (MeOH): λ_(max) (ε)=220 (44200 ), 298 nm (13200).

¹ H NMR ([D₆ ]DMSO): δ=0.87 (s, 9H, tBu), 2.12 (m, 1H, H-2'b), 2.41 (m,1H, H-2'a), 2.86 (s, 6H, N(CH₃)₂), 3.64 (m, 2H,H-5'a,b), 3.78 (m, 1H,H-4'), 4.33 (m, 1H, H-3'), 5.22 (d, J=4.5 Hz, 1H, 3'-OH), 6.20 (pt,J=6.6 Hz, 1H, H-1'), 6.30 (d, J=3.3 Hz, 1H, H-3), 6.36 (d, J=7.4 Hz, 1H,H-), 6.82 (t, J=7.4 Hz, 1H, H-6), 7.01 (d, J=7.4 Hz, 1H,H-), 7.18 (d,J=3.3 Hz, 1H, H-2), 7.20-7.50 (m, 10 phenyl-H), 7.64 (s, 1H,N═CH). C₃₃H₃₉ N₃ O₃ Si (553.78) calc. C 71.57%; H 7.10%; N 7.59% found 71.45%;7.21%; 7.72%

f)4-{[(Dimethylamino)-methylene]-amino}-1-[2-desoxy-5-O-(tert.-butyl-diphenylsilyl)-3O-methyl-sulphonyl-β-D-erythro-pentofuranosyl]-1H-indole.

800 mg (1.44 mmol) of the compound obtained in e) are dissolved inCH₂Cl₂ (24 ml) and the solution mixed with pyridine (5.5 ml). With icecooling, methanesulphonyl chloride (2.17 ml, 28.5 mmol) are addeddropwisethereto and the mixture stirred at RT (4 h). After the additionof MeOH (6.5 ml), it is diluted with CHCl₃ (100 ml) and extracted with0.1N HCl and H₂ O (in each case 100 ml). The org. phase is dried overNa₂ SO₄, filtered and the solvent evaporated in a vacuum. Afterchromatographic working up (silica gel 60H), one obtains 310 mg (34%) ofacolourless foam.

¹ H-NMR ([D₆ ]DMSO): δ=1.02 (s, 9H, t-Bu), 2.62 (m, 1H, H-2'b), 2.87 (m,1H, H-2'a), 3.00 (s, 6H, 2 CH₃), 3.32 (s, 3H, SCH₃), 3.82 (m, 2H, H-5'),4.26 (m, 1H, H-4'), 5.47 (m, 1H, H-3'), 6.40 (dd, J=6.1 and 8.1 Hz, 1H,H-1'), 6.47 (d, J=3.3 Hz, 1H, H-3), 6.51 (d, J=7.5 Hz, 1H,), 6.95 (pt,J=7.5 Hz, 1H, H-6), 7.20 (d, J=7.5 Hz, 1H, H-), 7.40 (m, aromat. H andH-2), 7.64 (m, aromat. H), 7.78 (s, N═CH).

g)4-[(Dimethylamino)-methylene]-amino-1-(2,3-didesoxy-2,3-didehydro-β-D-glyceropentofuranosyl)-1H-indole.

The compound obtained in f) (420 mg, 0.84 mmol) is dissolved in 50 mlTHF and the solution mixed with 10 ml Bu₄ NF (1M solution in THF). Onestirs the solution for 4 h at 50° C., evaporates the solvent in a vacuumand absorbs the residue on silica gel 60. After column chromatography(30×3 cm, CHCl₃ -MeOH (8:2) Rf=0.5), one obtainsa colourless oil.

¹ H-NMR ([D₆ ]DMSO): δ=3.01 (s, 6H, 2 CH₃), 3.46 (m, 2H, H2-5'), 4.77(m, 1H, H-4'), 4.91 (t, J=5.5 Hz, 1H, 5'-OH), 6.12 (m, 1H, H-2'), 6.49(m, 3H, H-3' and H-7/H-5 and H-3), 7.00 (m, 2H, H-6 and H-1'), 7.19 (d,J=3.3 Hz, 1H, H-2), 7.23 (d, J=8.4 Hz,1H, H-5/H-7), 7.81 (s, 1H, N═CH).

h)4-Amino-(2,3-didehydro-2,3-didesoxy-β-D-glyceropentofuranosyl)-1H-indole.

The compound obtained in g) (200 mg) is dissolved in MeOH (5 ml). Aftertheaddition of 20 ml conc. NH₃ (25%) one boils the solution underreflux.The solvent is evaporated in a vacuum and the residuechromatographed on silica gel (CHCl₃ /MeOH, 8:2, Rf=0.84; CH₂ Cl₂ /MeOH,95:5,Rf=0.40).

¹ H-NMR ([D₆ ]DMSO): δ=5.21 (s, NH₂), 6.91 (m, H-1'), 7.08 (d, J=3.4 Hz,H-2').

EXAMPLE 21-(2,3-Didehydro-2,3-didesoxy-β-D-glyceropentofuranosyl)-4-nitro-1H-indole.

a)1-[2-Desoxy-5-O-(tert.-butyldiphenylsilyl)-β-D-erythro-pentofuranosyl]-4-nitro-1H-indole.

1.43 (5.14 mmol) of the compound obtained in Example 1b are evaporated×2 with pyridine, dissolved in 30 ml pyridine, mixed with 1.57 ml (6.11mmol) TBDPSiC1 in the cold, stirred for 30 min at 0° C., stirred for 24h at RT, Py evaporated off, evaporated ×2 with toluene, adsorbed onsilica gel 60 (15 g). Chromatography (column 20×5 cm), Rf (CH₂ Cl₂)=0.2,yellow foam, yield: 1.73 g (65%). UV (MeOH): λ_(max) (ε)=241 (sh.11900), 338 (4600), 372 (6100).

¹ H-NMR ([D₆ ]DMSO): δ=0.96 (s, 9H, tBu), 2.30-264 (m, H-2'a,b), 3.79(m, 2H, H-5'2), 3.97 (m, 1H, H-4'), 4.53 (m, 1H, H-3'), 5.45 (d, J=4.5Hz, 1H, 3'-OH), 6.55 (pt, J=6.4 Hz, 1H, H-1'), 7.03 (d, J=3.1 Hz, 1H,H-3), 7.28-7.59 (m, 11 aromat. H), 7.90 (d, J=3.1 Hz, 1H, H-2), 8.10 (d,J=8.0 Hz, 1H, H-5), 8.15 (d, J=8.2 Hz, 1H, H-7). C₂₉ H₃₂ N₂ O₃ Si(516.67) calc. C 67.42%; H 6.24%; N 5.42% found 67.56%; 6.23%; 5.39%

b)1-[2-Desoxy-5-O-(tert.-butyldiphenylsilyl)-3-O-methylsulphonyl-β-D-erythro-pentofuranosyl]-4-nitro-1H-indole.

800 mg (1.55 mmol) of the compound obtained in a) are dissolved inCH₂Cl₂ (26 ml)/pyridine (6 ml). One mixes, while cooling, withmethanesulphonyl chloride (2.36 ml, 31 mmol), allows the mixture to warmslowly to RT and stirs for a further 4 h. One mixes with MeOH (1.7 ml),stirs for a further 15 min., dilutes with CHCl₃ (100 ml) andextractswith 0.1N HCl and H₂ O (in each case 100 ml). The organic phaseis dried over Na₂ SO₄. The solvent is evaporated in a vacuum.Afterchromatography (CH₂ Cl₂, column 30×4 cm, Rf 0.5), one obtains ayellow foam (840 mg, 91%). UV (MeOH): λ_(max) (ε)=235 (sh., 13300), 270(sh., 1800), 338 (5300), 365 (6300), 388(sh., 5100).

¹ H NMR ([D6]DMSO): δ=1.01 (s, 9H, t-Bu), 2.83 (m, 1H, H-2'b), 2.98 (m,1H, H-2'-a), 3.36 (s, 3H, S-CH₃), 3.86 (m, 2H, H-5'), 4.34 (m, 1H,H-4'), 5.53 (m, 1H, H-3'), 6.66 (pt, J=6.2 Hz, 1H, H-1'), 7.08 (d,J=3.3Hz, 1H, H-3), 7.30-7.62 (aromat. H, as well as H-6), 7.94 (d, J=3.3 Hz,1H, H-2), 8.14 (d, J=8 Hz, 1H, H-5), 8.23 (d, J=8 Hz, 1H, H-7). C₃₀ H₃₄N₂ O₇ SiS (594.76) calc. C 60.58%; H 5.76%; N 4.71%; S 5.39% found60.45%; 5.76%; 4.74%; 5.54%

c)1-(2,3-Didehydro-2,3-didesoxy-β-D-glyceropentofuranosyl)-4-nitro-1H-indole.

800 mg (1.35 mmol) of the compound obtained in b) are dissolved in 25 mlTHF, mixed with 5 ml Bu₄ NF (1M solution in THF) and the solutionstirred for 2 h at 50° C. under N₂ atmosphere. The solvent is evaporatedoff in a vacuum and the residue chromatographed on silica gel (column30×3.5 cm, elution agent CH₂ Cl₂ /MeOH 99:1. Rf 0.3). From the mainzone, after evaporating off of the solvent, one obtains a yellow oilwhich, upon leaving to stand, crystallises through. UV (MeOH): λ_(max)(ε)=237 (11700), 339 (sh., 4700), 370 (6100).

¹ H NMR ([D6]DMSO): δ=3.51 (m, 2H, H-5'), 4.86 (m, 2H, H-4' and 5'-OH),6.20 (pq, J=6.0 Hz and 1.7 Hz, 1H, H-2'), 6.54 (pq, J=6.0 Hz and J=1.6Hz, 1H, H-3'), 7.11 (d, J=3.3 Hz, 1H, H-3), 7.21 (m, 1H, H-1'), 7.40(t,J=8.1 Hz, 1H, H-6), 7.81 (d, J=3.3 Hz, 1H, H-2), 8.12 (d, J=8.1 Hz,1H,H-5), 8.27 (d, J=8.1 Hz, 1H, H-7). C₁₃ H₁₂ H₂ O₄ (260.25) calc. C60.00%; H 4.65%; N 10.76% found 60.18%; 4.76%; 10.69%

EXAMPLE 3 4-Amino-1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-1H-indole(1,3,7-tridesaza-2,3-didesoxyadenosine).

150 mg (0.58 mmol) of the compound obtained in Example 2c) are dissolvedin15 ml EtOH and hydrogenated in the presence of 15 mg Pd/C (10% Pd) for12 hat RT under atmospheric pressure. One filters and evaporates todryness. The residue is chromatographed on silica gel (Rf (CH₂ Cl₂/MeOH,97:3)=0.3).

¹ H NMR ([D6]DMSO): δ=1.91-2.40 (m, 4H, H-2' and H-3'), 3.49 (m,2H,H-5'), 4.04 (m, 1H, H-4'), 4.81 (t, J=5.5 Hz, 1H, 5'-OH), 5.20 (s, 2H,NH₂), 6.15 (dd, J=4.8 Hz and J=6.6 Hz, 1H, H-1'), 6.20 (d, J=7.5 Hz, 1H,H-5), 6.58 (d, J=3.3 Hz, 1H, H-3), 6.71 (d, J=7.5 Hz, 1H, H-7), 6.83 (t,7.5 Hz, 1H, H-6), 7.32 (d, J=3.3 Hz, 1H, H-2).

EXAMPLE 4 1-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-4-nitro-1H-indole.

a)5-O-[(1,1-Dimethylethyl)-dimethylsilyl]-2,3-didesoxy-α,β-D-glyceropentofuranosyl)chloride

5-O-[(1,1-dimethylethyl)-dimethylsilyl]-2,3-didesoxy-α,β-D-glyceropentofuranose(1.5 g, 6.5 mmol) [M. Okabe, R. -C. Sun, S. Y. -K. Tam, L. T. Todaro andD. L. Coffen, J. Org. Chem., 53, 4780, 1988) are dissolved in 26 mltetrahydrofuran and mixed with CCl₄ (1 ml) under N₂. One cools to -80°C. and mixes dropwise, in the course of 15 min, withtris-(dimethylamino)-phosphine (1.56 ml). After about 2 h, the sameamounts of CCl₄ and phosphine are again added thereto. After 6 h, theTLC(silica gel, EtOAc/petroleum ether, 2:8) shows an about 50% conversionof the lactol. The cold reaction solution of the halogenose isintroduced directly into the previously prepared glycosylation reaction.

b)1-(2,3-Didesoxy-5-O-(tert.-butyldimethylsilyl)-D-glyceropentofuranosyl)-4-nitro-1H-indole.

1.0 g (6.16 mmol) 4-nitroindole is dissolved in 200 ml MeCN and stirredfor20 min at RT, together with 690 mg (12.32 mmol) KOH and TDA-1. The insitu prepared cold solution of the halogenose obtained in a) (from 12.32mmol lactol) is injected portionwise into the suspension and thereaction mixture further stirred intensively for 45 min. Insolublecomponents are filtered off and the filtrate evaporated to dryness. Oneadsorbs on silicagel 60 (10 g) and chromatographs on silica gel 60H(petroleum ether/EtOAc, 8:2). Evaporation of the main zone provides ananomeric mixture in 60% yield which consists of 30% of the β-anomers and30% of the α-anomers.

¹ H NMR ([D₆ ]DMSO: δ=β-anomer: 4.16 (m, 1H, H-4'), 6.42 (dd, J=3.5 Hzand J=6.4 Hz, 1H, H-1'); α-anomer: 4.32 (m, 1H, H-4'), 6.47 (dd, H-1').C₁₉ H₂₈ N₂ O₄ Si (376.53) calc. C 60.61%; H 7.50%; N 7.44% found 60.77%;7.42%; 7.32%

c) 1-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-4-nitro-1H-indole.

The β-anomer obtained in b) is dissolved in THF. After the additionofBU₄ NF (1M solution in THF), one stirs for 30 min at roomtemperature.The solvent is evaporated in a vacuum and the residueadsorbed on silica gel 60. After column chromatography (CH₂ Cl₂ MeOH,97:3), one obtains the title compound as yellow oil. Rf (CH₂ Cl₂ -MeOH,97:3)=0.4.

¹ H-NMR ([D₆ ]DMSO): δ=4.11 (m, 1H, H-4'), 4.89 (t, J=5.4 Hz, 1H,5'-OH), 6.41 (dd, J=4.0 and 6.7 Hz, 1H, H-1'), 7.09 (d, J=3.2 Hz, 1H,H-3), 7.37 (pt, J=8.1 Hz, 1H, H-6), 8.04 (d, J=3.2 Hz, 1H, H-2).

EXAMPLE 4.11-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-4-nitro-1H-indole.

The β-anomer obtained in 4b is desilylated analogously to Example 4c.After column chromatography (CH₂ Cl₂ -MeOH, 97:3), one obtains the titlecompound as yellow oil, Rf=0.4.

¹ H-NMR ([D₆ ]DMSO: δ=4.27 (m, 1H, H-4'), 4.80 (t, J=5.7 Hz, 1H, 5'-OH),6.49 (dd, J=4.2 Hz and 6.3 Hz, 1H, H-1'), 7.09 (d, J=3.2 Hz, 1H, H-3),7.38 (pt, J=8.1 Hz, 1H, H-6), 7.93 (d, J=3.2 Hz, 1H, H-2).

EXAMPLE 5 1-(2,3-Didesoxy-β-D-glyceropentofuranosyl)benzimidazole.

a)1-[2-Desoxy-3,5-di-O-(4-methylbenzoyl)-β-D-erythrofuranosyl]-benzimidazole.

The glycosylation of benzimidazole with2-desoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride tookplace under the same conditions as described in Example 4b. Data see [Z.Kazimierczuk, R. Stolarski and D. Shugar, Z. Naturforsch., 40c, 715(1985)].

b) 1-(2-desoxy-β-D-erythro-pentofuranosyl)benzimidazole.

The preparation of this substance takes place from the compound obtainedina) by detoluoylation Lit. as in a).

c)1-[2-Desoxy-5-O-(tert.-butyldimethylsilyl)-β-D-erythro-pentofuranosyl]-benzimidazole.

1.0 g (4.26 mmol) of the compound obtained in b) is evaporated 2× withpyridine and subsequently dissolved in 20 ml pyridine. In the cold (0°C.), 1.3 ml (1.391 g, 5.06 mmol) TBDPSiCl are added thereto andthesolution stirred for 30 min at 0° C. One allows to warm up slowly toroom temperature and stirs for a further 24 h.

Chromatography (column 25×4 cm/silica gel 60) gives a colourlessoil;treatment with diethyl ether gives colourless crystals of the m.p.144°-145° C., Rf (CHCl₃ /MeOH 9:1)=0.45. Yield: 1.24 g (61%). UV (MeOH):λ_(max) (ε)=246 (7500), 252 (sh. 7200),265 (4800), 273 (4900), 281(4200).

¹ H NMR ([D6]DMSO): δ=0.94 (s, 9H, 3 CH₃), 2.35 (m, 1H, H-2'b), 2.65 (m,1H, H-2'a), 3.77 (m, 2H, H-5'), 3.94 (m, 1H, H-4'), 4.49 (m, 1H, H-3'),5.44 (d, J=4.1 Hz, 1H, 3'-OH), 6.37 (pt, J=6.5 Hz, 1H, H-1'), 7.10-7.66(m, 14 aromat. H), 8.36 (s, 1H, H-2). C₂₈ H₃₂ N₂ O₃ Si (472.66) calc. C71.15%; H 6.82%; N 5.93% found 71.23%;6.85%; 5.94%

d)1-[2-Desoxy-5-O-(tert.-butyldimethylsilyl)-3-O-phenoxythiocarbonyl-β-D-erythro-pentofuranosyl]benzimidazole.

500 mg (1.06 mmol) of the compound obtained in c) in anhydrous MeCN (20ml)are stirred for 16 h at RT with 4-(dimethylaminopyridine (DMAP, 768mg, 6.36 mmol) and phenoxythiocarbonyl chloride (PTC-Cl, 320 μl, 1, 2.34mmol). After evaporating off of the solvent, one chromatographs onsilica gel 60 H and, from the main zone, obtains a colourless foam (480mg, 74%).Rf (CH₂ Cl₂ /acetone, 95:5)=0.5. UV (MeOH): λ_(max) (ε)=243(12000), 264 (sh., 5100), 273 (4800), 280 (4100).

¹ H NMR ([D6]DMSO): δ=1.03 (s, 9H, 3 CH₃), 2.88 (m, 1H, H-2'b), 3.06 (m,1H, H-2'a), 3.99 (m, 2H, H-5'), 4.48 (m, 1H, H-3'), 6.55 (dd, J=5.4 and9.0 Hz, 1H, H-1'), 7.09-7.84 (m, 19 aromat. H), 8.46 (s, 1H, H-2). C₃₅H₃₆ N₂ O₄ SSi (608.84) calc. 69.05%; H 5.96%; N 4.60%; S 5.27% found69.26%; 5.99%; 4.74%; 5.12%

e)1-[2,3-Didesoxy-5-O-(tert.-butyldimethylsilyl)-β-D-glyceropentofuranosyl]-benzimidazole.

A solution of 350 mg (0.57 mmol) of the compound obtained in d) inanhydrous toluene (20 ml) is stirred in the presence of AIBN (35 mg) andtributyl tin hydride (200 μl) for 3 h at 80° C. under an atmosphere ofargon. Chromatographic working. Yield 83%. Rf (CH₂ Cl₂ /acetone) 0.4. UV(MeOH): λ_(max) (ε)=247 (7300), 251 (sh., 7100), 265 (4600), 273 (4700),281 (4100).

¹ H NMR ([D6]DMSO): δ=0.96 (s, 9H, 3 CH₃), 2.13 (m, 2H, H-3'), 2.47 (m,2H, H-2'), 3.74 (m, 2H, H-5'), 4.26 (m, 1H, H-4'), 6.32 (pt, J=4.8 Hz,1H, H-1'), 7.22-7.71 (m, 14 aromat. H), 8.42 (s, 1H, H-2). C₂₈ H₃₂ N₂ O₂Si (456.66) calc. C 73.65%; H 7.06%; N 6.13% found 73.64%; 7.02%; 6.10%

f) 1-(2,3-Didesoxy-β-glycerpentofuranosyl)benzimidazole.

The compound (200 mg) obtained in a) is dissolved in THF mixed with Bu₄NF (1M solution in THF) and stirred for 30 min at RT. Evaporationof thesolvent and chromatographic working up gives a colourless oil(yield69%).

¹ H NMR ([D6]DMSO: δ=2.06 (m, 2H, H-3'), 2.36 (m, 2H, H-2'), 3.55 (m,2H, H-5'), 4.14 (m, 1H, H-4'), 4.93 (m, 1H, 5'-OH), 6.28 (dd, J=4.1 and6.5 Hz, 1H, H-1'), 7.27 (m, 2H, H-5 and H-6), 7.68 (m, 2H, H-4 and H-7),8.51 (s, 1H, H-2).

EXAMPLE 6 1-(2,3-Didesoxy-β-D-glyceropentofuranosyl)benzimidazole.

a) One also obtains the title compound described in Example 5analogously to Example 2b in that one dissolves 1.0 g (8.48 mmol)benzimidazole in 200ml MeCN and stirs with KOH (1.9 g) and TDA-1 (0.8mmol) for 15 min at RT. The in situ prepared cold solution of thehalogenose (prepared from 17 mmol lactol) is injected portionwise intothe mixture. One further stirs for 30 min at RT, filters and evaporatesthe solvent in a vacuum. The residue is chromatographed on silica gel60. One obtains the α-anomer in 30% yield and the β-anomer in 30% yield.

¹ H NMR ([D₆ ]DMSO: β-anomer: δ=4.17 (m, 1H, H-4'), 6.26 (dd, 1H, H-1'),8.42 (s, 1H, H-2); α-anomer: δ=4.34 (m, 1H, H-4'), 6.33 (pt, 1H, H-1'),8.38 (s, 1H, H-2).

b) After splitting off of the silyl protective group analogously toExample2c), one obtains the title compound.

EXAMPLE 71-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-1H-pyrrolo[2,3-b]pyridine.

a)1-[2'-Desoxy-5-O-(triphenylmethyl)-β-D-erythropentofuranosyl]-1H-pyrrolo[2,3-b]pyridine.

1.48 g (6.3 mmol)1-(2-desoxy-β-D-erythropentofuraosyl)-1H-pyrrolo[2,3-b]pyridine [F.Seela and R. Gumbiowski, Heteocycles, 29,795 (1989)] is evaporated twicewith, in each case, 30 ml dry pyridine. Subsequently, under argon, oneadds thereto 3.55 g (12.6 mmol) triphenylmethyl chloride, as well as 3.3ml (19 mmol) Hunig base and stirs for 4 h at room temperature.

The reaction mixture is added to 200 ml 5% aqueous NaHCo₃ and extractedthree times with, in each case, 150 ml CH₂ Cl₂. The combined organicphases are dried with Na₂ SO₄, filtered and chromatographed on silicagel 60 H (column 7×4.5 cm, CH₂ Cl₂ /acetone, 8:2). After the evaporationof the main zone, one obtains a colourless foam; 1.75 g (58%). TLC(silica gel, CH₂ Cl₂ /acetone, 8:2) Rf 0.8. UV (MeOH): λ_(max) =288 nm(ε=7600).

¹ H NMR ([D₆ ]DMSO): δ=2.28 (m, 2'-Ha); 2.61 (m, 2'-Hb); 3.17 (d, J=4.8Hz, 5'-H2); 3.97 (m, 4'-H), 4.39 (m, 4'-H), 5.38 (d, J=4.7 Hz, 3'-OH),6.53 (d, J=3.6 Hz, 3'-H), 6.76 (pt, J=4.0 Hz, 1'-H), 7.13 (dd,J=7.8 Hz,5-H), 7.59 (d, J=3.7 Hz, 2-H), 7.97 (dd, J=7.8 Hz, 4-H), 8.24 (dd, J=1.5Hz, J=4.7 Hz, 6-H). C₃₁ H₂₈ N₂ O₃ (476.58) calc. C 78.13%; H 5.92%; N5.88% found C 78.06%; H 6.04%; N 5.79%

b)1-(2-Desoxy-5-O-triphenylmethyl-3-O-phenoxythiocarbonyl-β-D-erythro-pentofuranosyl)-1H-pyrrolo[2,3-b]pyridine.

A solution of 1.75 g (3.7 mmol) of the compound obtained in a) in 50 mlabs. acetonitrile is mixed under argon with 1.12 g (9.2 mmol)4-(dimethylamino)pyridine and 1.0 ml (7.4 mmol) phenoxythiocarbonylchloride and stirred for 48 h at room temperature. After the evaporationof the reaction mixture, the residue is chromatographed on silica gel 60H(column 10×4 cm, (CH₂ Cl₂). From the main zone are obtained1.2 g (51%)of a colourless foam. UV (MeOH): λ_(max) =285 (ε=8600).

¹ H-NMR ([D₆ ]DMSO: δ=2.77 (m, 2'-Ha), 3.18 (m, 2'-Hb), 3.38 (m, 5'-H2),4.42 (m, 4'-H), 5.93 (m, 3'-H), 6.62 (d, J=3.7 Hz, 3-H), 6.81 (dd, J=5.5Hz, J=9.1 Hz, 1'-H), 7.18 (dd, J=4.7 Hz, J=7.8 Hz, 5-H), 7.67 (d, J=3.7Hz, 2-H), 8.03 (dd, J=1.4 Hz, J=7.8 Hz, 4-H), 8.24 (dd, J=1.4 Hz, J=4.7Hz, 6-H) and other arom. protors. C₃₈ H₃₂ N₂ O₄ S (612.74) calco C74.49%; H 5.26%; N found C 74.65% H 5.41%; N 4.35%

c)1-(2,3-Didesoxy-5-O-triphenylmethyl-β-D-glyceropentofuranosyl)-1H-pyrrolo[2,3-b]pyridine.

A solution of 1.2 g (1.86 mmol) of the compound obtained in b) in 60 mlabsolute toluene is mixed under argon with 90 mg (0.6 mmol) AIBN and 1.1ml (4 mmol) tributyl tin hydride and stirred for 5 h at 80° C. After theevaporation of the reaction mixture, the residue is chromatographed onsilica gel 60 H (column 8×3 cm, CH₂ Cl₂). From the main zone is obtained0.8 g (93%) of amorphous product. Recrystallisation from i-PrOH givescolourless needles of the m.p. 115° C. TLC (silica gel, CH₂ Cl₂/acetone, 95:5), Rf: 0.83. UV (MeOH): λ_(max) =289 nm (ε=8100).

¹ H-NMR ([D₆ ]DMSO): δ=2.08 (m, 3'-H2), 2.37 (m, 2'-H2), 3.12 (m, 5'-H),4.24 (m, 4'-H), 6.48 (d, J=3.7 Hz, 3-H), 6.63 (dd, J=4.0 Hz, J=6.9 Hz,1'-H), 7.13 (dd, J=4.7 Hz, J=7.8 Hz, 5-H), 7.61 (d, J=3.7 Hz, 2-H), 7.97(dd, J=1.5 Hz, J=7.8 Hz, 4-H), 7.26 (dd, J=1.5 Hz, J=4.7 Hz, 6-H) andother atom. protons. C₃₁ H₂₈ N₂ O₂ (460.58) calc. C 80.84%; H 6.13%; N6.08% found C 80.79%; H 6.16%; N 6.14%

d) 1-(2,3-Didesoxy-β-D-glycerqpentofuranosyl)-1H-pyrrolo[2,3-b]pyridine.

240 mg (0.52 mmol) of the compound obtained in c) are mixed with 30 ml80% acetic acid and stirred for 3 h at room temperature. The solvent isstripped off under oil pump vacuum and the residue evaporatedsubsequentlyseveral times with water. The residue is chromatographed onsilica gel 60 H(column 8×3 cm, CH₂ Cl₂ /ethyl acetate, 95:5). Theresidue of the main zone is recrystallised from water. 102 mg (90%) ofcolourless crystals of the m.p. 124°-125° C. UV (MeOH): λ_(max) =288 nm(ε=7500).

¹ H-NMR ([D₆ ]DMSO): δ=2.08 (m, 3'-H2), 2.31 (m, 2'-H2), 3.56 (m,5'-H2), 4.08 (m, 4'-H), 4.98 (tr, J=5.5 Hz, 5'-OH), 6.54 (d, J=3.2 Hz,3-H), 6.59 (pt, J=5.4 Hz, 1'-H), 7.13 (dd, J=4.7 Hz, J=7.7 Hz, 5-H),7.77 (d, 1H, J=3.2 Hz, 2-H), 7.98 (d, J=7.7 Hz, 4-H) , 8.25 (d, J=4.8Hz, 6-H). C₁₂ H₁₄ N₂ O₂ (218.26) calc. C 66.04%;H 6.47%; N 12.83% foundC 66.09%; H 6.57%; N 12.84%

EXAMPLE 81-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)-4-nitro-1H-pyrrolo[2,3-b]pyridine.

a)1-[5-O-((1,1-dimethylethyl)-diphenylsilyl)-(2'-desoxy-β-D-erythro-pentofuranosyl)]-4-nitro-1H-pyrrolo[2,3-b]pyridine.

1.0 g (3.6 mmol)1-(2-desoxy-β-D-erythropentofuranosyl)-4-nitro-1H-pyrrolo[2,3-b]pyridine[F. Seela and R. Gumbiowski, Heterocycles, 29,795 (1989)] isevaporatedtwice with, in each case, 30 ml dry pyridine, dissolved in 50ml pyridine and cooled under N₂ to 0° C. 1.18 ml (4.6 mmol)1,1-dimethylethyldiphenylsilyl chloride are now injected in through aseptum. Subsequently, one removes the cold bath and leaves to stir for 8hat room temperature. The reaction mixture is evaporated, the residue istaken up in 200 ml CHCl₃, washed twice with, in each case, 40 ml 0.1NHCland subsequently with a little water and dried over Na₂ SO₄. The solventis stripped off and the yellow oil remaining behind is chromatographedon silica gel 60 (column 10×3 cm, CH₂ Cl₂ /acetone, 95:5). From the mainzone one obtains, after evaporation, 1.5 g (81%) of a yellow foam. UV(MeOH): λ_(max) =357, 338 nm (ε=4400, 4400).

¹ H-NMR ([D₆ ]DMSO): δ=0.99 (s, CH₃), 2.38 (m, 2'-Hb),2.63 (m, 2'-Ha),3.75 (dd, J=4.8 Hz, 10.9 Hz, 5'-H), 3.87 (dd, J=4.8 Hz, 10.9 Hz, 5'-H),3.96 (m, 4'-H), 4.53 (m, 3'-H), 5.46 (d, J=4.4 Hz, 3'-OH),6.79 (tr,J=6.6 Hz, 1'-H), 6.98 (d, J=3.6 Hz, 3-H), 7.97 (d, J=5.3 Hz, 5-H), 8.07(d, J=3.6 Hz, 2-H), 8.53 (d, J=5.3 Hz, 6-H) and other arom. protons. C₂₈H₃₁ N₃ O₅ Si (517.66) calc. C 64.97%; H 6.04%; N 8.12% found C 65.00%; H6.24%; N 8.01%

b)1-[2-Desoxy-5-O-((1,1-dimethylethyl)-diphenylsilyl)-3-O-methylsulphonyl-(.beta.-D-erythro-pentofuranosyl)]-4-nitro-1H-pyrrolo[2,3-b]pyridine.

To a solution of 1.0 g (1.9 mmol) of the compound obtained in a) in 50ml CH₂ Cl₂ one adds 1 ml (13 mmol) methanesulphonic acid chloride and 15ml pyridine and leaves to stir for 12 h. After ending of the reaction(TLC monitoring), one adds 20 ml methanol thereto and further stirs for15 min. The reaction mixture is evaporated, the residue mixed with 200ml CHCl₃, washed twice with, in each case, 40 ml 0.1N HCl andsubsequently with a little water and dries over Na₂ SO₄. Thesolvent isstripped off and the yellow oil remaining behind chromatographedonsilica gel 60 (column 8×3cm, CH₂ Cl₂). From the evaporation residue ofthe main zone, one obtains a colourless substance which foams in thecase of evaporation. 1.04 g (90%). UV (MeOH): λ_(max) =352, 338nm(ε=4400, 4700).

¹ H-NMR ([D₆ ]DMSO): δ=0.99 (s, CH₃, 2.80 (m, 2'-Ha), 3.11 (m, 2'-Hb),3.90 (m, 5'-H2), 4.32 (m, 4'-H), 5.54 (m, 3'-H), 6.28 (pt, J=6.3 Hz,1'-H), 7.02 (d, J=4.9 Hz, 3-H), 7.98 (d, J=6.5 Hz, 5-H), 8.09 (d, J=4.9Hz, 2-H), 8.52 (d, J=5.3 Hz, 6-H) and other arom. protons. C₂₉ H₃₃ N₃ O₇SSi (595.74) calc. C 58.47%; H 5.58%; N 7.03% found C 58.69%; H 5.65%; N7.03%

c)1-(2,3-Didesoxy-β-D-glyceropent-2-enofuranosyl)-4-nitro-1H-pyrrolo[2,3-b]pyridine.

To a solution of 400 mg (0.67 mmol) of the compound obtained in b) in 10mlTHF one adds 5 ml 1M tetrabutylammonium fluoride in THF and leaves tostir under reflux for 4 h. The solvent is stripped off in a vacuum andthe crude product chromatographed on silica gel 60 (column 10×3 cm, CH₂Cl₂ /MeOH; 95:5). The evaporation residue is crystallised fromisopropanol. 120 mg (68%) of yellow needles of the m.p. 154° C. UV(MeOH): λ_(max) =358, 338 nm (ε=5000, 4700).

¹ H-NMR ([D₆ ]DMSO): δ=3.57 (m, 5'-H2), 4.87 (m, 4'-H), 4.96 (tr, J=5.4Hz, 5'-OH), 6.14 (m, 2'-H), 6.52 (m, 3'-H), 7.05 (d, J=3.6Hz, 3-H), 7.40(m, 1'-H), 7.99 (d, J=5.3 Hz, 5-H), 8.03 (d, J=3.6 Hz, 2-H),8.58 (d,J=5.3 Hz, 6-H). C₁₂ H₁₁ N₃ O₄ (261.24) calc. C55.17%; H 4.24%; N 16.09%found C 55.27%; H 4.38%; N 16.03%

Example 94-Amino-1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-1H-pyrrolo[2,3-b]pyridine.

50 mg of the compound obtained in Example 8c) are dissolved in 30 mlmethanol and mixed with 0.1 ml pyridine and 10 mg Pd/C (10% Pd). It ishydrogenated for 2 hours at room temperature under normal pressure. Theend product is indicated by decolorisation of the solution. The catalystis filtered off, washed several times with methanol, the filtrateevaporated and the residue chromatographed on silica gel 60 (column8×1.5 cm, CH₂ Cl₂ /MeOH, 9:1). From the main zone, one obtains 10 mg(22%) of the colourless title compound.

¹ H-NMR ([D₆ ]DMSO): δ=1.99 (m, 3'-H2), 2.27 (m, 2'-H2), 3.50 (m,5'-H2), 4.03 (m, 4'-H), 6.16 (d, J=5.4 Hz, 5-H), 6.25 (s, NH₂), 6.34(pt, J=5.98 Hz, 1'-H), 6.52 (d, J=3.6 Hz, 3-H), 7.28 (d, J=3.6 Hz, 2-H),7.69 (d, J=5.4 Hz, 6-H).

EXAMPLE 101-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-1H-pyrrolo[2,3-b]pyridine5'-triphosphate,triethylammonium salt.

21.8 mg (0.1 mmol) of the compound obtained in Example 7d are dissolvedin 250 μl (2.14 mmol) trimethyl phosphate and mixed with 11.7 μl (0.13mmol) of freshly distilled POCl₃ at 4° C. After stirring for 1.5 h at 4°C., a solution of 0.5 mmol bis-(tri-n-butylammonium) pyrophosphate in 1ml DMF and 100 μl (0.42 mmol) tri-n-butylamine is added thereto. After 1min, it is neutralised with 1M aqueous triethylammonium bicarbonatesolution (TBK) and subsequently the solvent is stripped off in a vacuum.The residue is taken up in 150 ml water and adsorbed on Fraktogel TSK(column: 30×2.6 cm). Gradient elution (360ml H₂ O/360 ml 0.5M TBKsolution) leads, at 0.49M TBK, to a main zone from which, afterevaporation of the solvent, 370 A₂₈₈ units (49%) ofcolourless, amorphoustriphosphate are obtained in the form of the triethylammonium salt. TLC(2-propanol/NH₃ /H₂ O: 3:1:1). Rf=0.12; HPLC (LiChrosorb RP-18; 0.1Mammonium acetate/50% acetonitrile: 1ml/min); Rt=1.95 min; UV (MeOH):λ_(max) =288 nm (ε=7500).

³¹ P-NMR (D₂ O; 0.1M tris-HCl (1:1), pH 7.0, 100 mM EDTA): δ=-10.32 (d,J=19 Hz, Pα), -22.04 (t, J=19 Hz, Pβ), -7.46(d, J=19 Hz, P gamma).

EXAMPLE 111-(2,3-Didesoxy-β-D-glyceropent-2-enofuranosyl)-4-nitro-1H-pyrrolo[2,3-b]pyridine5'-triphosphate, triethylammonium salt.

26 mg (0.1 mmol) of the compound obtained in Example 8c) werephosphorylated as described in Example 10 and worked up. TLC(2-propanol/NH₃ /H₂ O, 3:1:1); Rf=0.12. HPLC (LiChrosorb RP-18; 0.1Mammonium acetate 50% acetonitrile; 1 ml/min); Rt=1.91 min; yield 180A₃₅₈ units (36%) of colourless, amorphous product. UV (MeOH): λ_(max)=358 nm(ε=5000).

³¹ P-NMR (D₂ O, 0.1M tris-HCl (1:1), pH 7, 100 mM EDTA): δ=-10.52 (d,J=20 Hz, Pα), -21.75 (t, J=20 Hz, Pβ), -6.18(d, J=20 Hz, P gamma).

EXAMPLE 128-(2,3-Didesoxy-α(β)-D-glyceropentofuranosyl)-8H-imidazo[1,2-a]-s-triazin-4-one.

a)8-{5-O-[(1,1-Dimethylethyl)-dimethylsilyl]-2,3-didesoxy-α(β)-D-glyceropentofuranosyl}-2-[(2-methylpropionyl)-amino]-8H-imidazo[1,2-a]-s-triazine-4-one.

2-[(2-Methylpropionyl)-amino]-8H-imidazo[1,2-a]-s-triazin-4-one (500 mg,2.26 mmol) are dissolved in dry MeCN (100 ml) with gentle warming andmixed with K₂ CO₃ (1 g). One adds TDA-1 (50 μl) thereto and leaves thereaction mixture to stir for 10 min at RT. Subsequently, the coldsolution of the5-O-[(1,1-dimethylethyl)-dimethylsilyl]-2,3-didesoxy-D-glyceropentofuranosylchloride prepared according to Example 4a) is added thereto in eightequal portions at intervals of 2-3 min and the reaction mixture furtherstirred for 30 min at RT under N₂. Thin layer chromatographic reactionmonitoring (silica gel, CH₂ Cl₂ -MeOH, 9:1) shows a complete reaction togive two products. After filtration through Celite (1cm), it isevaporated at oil pump vacuum (20°-25° C.) and theresidue immediatelychromatographed on silica gel 60 H (column: 6×25 cm, CH₂ Cl₂ -MeOH,95:5). From the rapidly moving main zone, oneobtains the anomericmixture which is dissolved in CH₂ Cl₂ -MeOH 99:1 and againchromatographed on silica gel 60 H (column: 6×15 cm, CH₂ Cl₂ -MeOH 99:1(11), CH₂ Cl₂ -MeOH 97:3 (2 1). From the more rapidly moving zone (Rf(silica gel, CH₂ Cl₂ -MeOH9:1) 0.90), one obtains, after evaporation,250 mg (25%) of the β-anomer as a colourless foam.

¹ H-NMR ([D₆ ]DMSO): δ=10.33 (s, NH), 7.64 (d, J=2.7 Hz, H-7), 7.58 (d,J=2.7 Hz, H-6), 6.14 (pt, J=3.8 Hz, H-1'), 4.14 (m, H-4'), 3.75 (m, H₂-5'), 2.92 (m, CH), 2.40 (m, H₂ -2'), 2.06 (m, H₂ -3'), 1.07 and 1.05 (2s, iBu-Me), 0.84 (s, t-Bu-Me), 0.01 (s, Si-Me).

From the more slowly moving zone (Rf (silica gel, CH₂ Cl₂ -MeOH 9:1)0.85), one obtains, after evaporation, 270 mg (27%) of the β-anomer as acolourless foam.

¹ H-NMR ([D₆ ]DMSO): δ=10.3 (s, NH), 7.66 (d, J=2.7 Hz, H-7), 7.59 (d,J=2.7 Hz, H-6), 6.19 (dd, J=5.8 Hz, H-1'), 4.51 (m, H-4'), 3.62 (m, H₂-5'), 2.94 (m, CH), 2.35 and 1.82 (m, H₂ -2' and H₂ -3'), 1.07 and 1.05(2 s, iBu-Me), 0.88 (s, t-Bu-Me), 0.05 (s, Si-Me).

b)2-[(2-Methylpropionyl)-amino]-8-(2,3-didesoxy-β-D-glyceropentofuratosyl-8H-imidazo[1,2-a]-s-triazin-4-one.

The β-anomer isolated according to Example 12a is dissolved in dry THF(5ml) and mixed with Bu₄ NF (1M in THF, 5 ml). One stirs for 10 min at RT,evaporates to a colourless oil and chromatographs on silica gel 60 H(column: 10×6 cm, 1 l CH₂ Cl₂ -MeOH 97:3; 1 l CH₂ Cl₂ -MeOH 9:1). Fromthe main zone, one obtains the product (110 mg, 93%) as colourless foam.TLC (silica gel, CH₂ Cl₂ -MeOH 9:1): Ref=0.3.

¹ H-NMR ([D₆ ]DMSO): δ=10.32 (s, NH), 7.77 (d, J=2.7 Hz, H-7), 7.58 (d,J=2.7 Hz, H-6), 6.14 (dd, J=6.4 Hz, 3.7 Hz, H-1'), 4.99 (t,J=5.4 Hz,5'-OH), 4.11 (m, H-4'), 3.58 (m, H₂ -5'), 2.93 (m, J=6.8 Hz), 2.38 (m,H₂ -2'), 2.03 (H₂ -3'), 1.07 and 1.05 (2 CH₃).

c)2-[(2-Methylpropionyl)-amino]-8-(2,3-dideoxy-α-D-glyceropentofuranosyl-8H-imidazo[1,2-a]-s-triazin-4-one.

The α-anomer isolated according to Example 12a reacted as described inExample 12b and worked up. TLC (silica gel, CH₂ Cl₂ -MeOH 9:1) Rf=0.3.

¹ H-NMR ([D₆ ]DMSO): δ=10.34 (s, NH), 7.67 (d, J=2.6 Hz, H-7), 7.59 (d,J=2.6 Hz, H-6), 6.21 (dd, J=6.5 Hz, 3.8 Hz, H-1'), 4.83 (t,J=5.4Hz,5'-OH), 4.12 (m, H-4'), 3.43 (m, H₂ -5'), 2.90 (m, J=6.9 Hz, CH), 2.3(m, H₂ -2'), 1.85 and 1.58 (H₂ -3'), 1.07 and 1.05 (2 CH₃).

d)8-(2,3-Dideoxy-β-D-glyceropentofuranosyl-8H-imidazo[1,2-a]-s-triazin-4-one.

The β-anomer isolated according to Example 12b (75 mg, 0.23 mmol) isdissolved in methanolic ammonia (5 ml) and stirred for 2 h at RT. Oneevaporates and chromatographs the oily residue on silica gel 60 H(column 6×6 cm; elution agent CH₂ Cl₂ -MeOH 9:1). After evaporation ofthe main zone, one obtains 40 mg (70%) of product as colourless crystalsof the m.p. 157°-158° C. (MeOH). TLC (silica gel, CH₂ Cl₂ -MeOH 9:1)Rf=0.2.

¹ H-NMR ([D₆ ]DMSO): δ=7.50 (d, J=2.7 Hz, H-7), 7.34 (d, J=2.7, H-6),6.03 (dd, J=5.8 Hz, 3.4 Hz, H-1'), 4.99 (t, J=5.8 Hz, 5'-OH),4.06 (m,H-4'), 3.57 (m, H₂ -5'), 2.3 (m, H₂ -2'), 1.97 (m, H₂ -3').

e)8-(2,3-Dideoxy-α-D-glyceropentofuranosyl-8H-imidazo[1,2-a]-s-triazin-4-one.

The α-anomer isolated according to Example 12c is reacted and worked upas described in Example 12d. The oily residue is chromatographed onsilica gel 60 (column 15×6 cm, elution agent: 1 l CH₂ Cl₂ -MeOH 95:5; 2l CH₂ Cl₂ -MeOH 9:1). After evaporation of the main zone, one obtains 60mg (74%) of product as colourless foam. TLC (silica gel, CH₂ Cl₂ -MeOH9:1): Rf=0.2.

¹ H-NMR([D₆ ]DMSO): δ=7.39 (d, J=2.7 Hz, H-7), 7.35 (d, J=2.7 Hz, H-6),6.92 (s, br., NH₂), 6.10 (dd, J=3.6 Hz, 6.3 Hz, H-1'), 4.81 (t, J=5.7Hz, 5'-OH), 4.33 (m, H-4'), 3.40 (m, H₂ -5'), 2.40 and 2.20 (2 m, H₂-2'), 2.20 and 1.83 (2 m, H₂ -3').

EXAMPLE 13 7-Methoxy-1(2),(3)-(2',3'-didesoxy-α(β)-D-erythropentofuranosyl)-3H-1,2,3-triazolo[4,5d]pyrimidine.

a) To a suspension of powdered KOH (750 mg, 14.3 mmol) in anhydrous MeCN(50 ml) are added at intervals of, in each case, 10 min, TDA-1 (40 μl,0.12 mmol) and 7-methoxy-3H-1,2,3-triazolo[4,5-d]pyrimidine (900 mg, 6mmol). After a further 10 min, within the course of 30 min, is added, in5ml portions, a cold solution of thet-butyl-dimethylsilyl-2',3'-didesoxy-D-ribofuranosyl chloride (12 mmol),prepared according to Example 4a, in 30 ml THF. The reaction mixture isstirred for a further 30 min, insoluble material filtered off and thefiltrate evaporated to dryness at 40° C. under oil pump vacuum.Thesyrupy residue is immediately flash chromatographed (silica gel 60,column:30×3 cm, petroleum ether:ethyl acetate, 6:4). One obtains 3 mainfractions (I, II, III). Fraction I contains 4 compounds which areseparated by multiple chromatography (silica gel 60, column: 25×3 cm,dichloromethane:acetone, 95:5; and column 30×3 cm, petroleum ether:ethylacetate, 7:3). Fractions II and III each contain one compound.Theassignment of the regio- and stereoisomers took place by comparison ofthe ¹³ C-NMR data with that of the corresponding desoxy compounds(F.Seela et al., Heterocyclus, 1989, 29, 2193).

b)7-Methoxy-3-(5'-t-butyldimethylsilyl-2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

The most rapid zone of Fraction I (see 13a) gives 202 mg (9.2%) ofproduct as colourless oil. TLC (silica gel, petroleum ether:ethylacetate, 7:3) Rf=0.6.

¹ H-NMR ([D₆ ]DMSO): δ=0.033 and 0.049 (2 s, 2 SiCH₃),0.86 (s,SiC(CH₃)₃), 1.97 (m, 3'-H), 2.66 (m, 2'-H), 3.66 (m, 5'-H), 4.21 (s,OCH₃), 4.40 (m, 4'-H), 6.72 (dd, J=6.8 Hz and 3.3 Hz,1'-H), 8.76 (s,5-H).

c)7-Methoxy-3-(5'-t-butyldimethylsilyl-2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

From the middle zone of Fraction I (see 13a), one obtains 195 mg (8.9%)of product as colourless oil. TLC (silica gel, dichloromethane:acetone,95:5)Rf=0.65.

¹ H-NMR ([D₆ ]DMSO): δ=-0.194 and -0.15 (2 s, 2 SiCH₃), 0.72 (s,SiC(CH₃)₃), 2.21 (m, 3'-H), 2.59 and 2.81 (m, 2'-H), 3.55 (dd, J=11.0 Hzand 5.9 Hz, 5'-H), 4.21 (s, OCH₃), 4.26 (m, 4'-H), 6.67 (dd, J=7.1 Hzand 1.7 Hz, 1'-H), 8.79 (s, 5-H).

d)7-Methoxy-2-(5'-t-butyldimethylsiyl-2',3'-didesoxyα-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

The slowest zone of Fraction I (see 13a) (referred to the elution agentdichloromethane:acetone, 95:5) separates after renewed chromatography(elution agent petroleum ether:ethyl acetate, 7:3) into two sub-zones.Themore rapid sub-zone gives 172 mg (7.8%) of product as colourless oil.TLC (silica gel, petroleum ether:ethyl acetate, 7:3) Rf=0.5.

¹ H-NMR ([D₆ ]DMSO: δ=0.058 and 0.065 (2 s, 2 SiCH₃), 0.86 (s,SiC(CH₃)₃), 1.96 (m, 3'-H), 2.5 (m, 2'-H), 3.68 (m, 5'-H), 4.18 (s,OCH₃), 4.50 (m, 4'-H), 6.67 (dd, J=5.9 Hz and 2.7 Hz,1'-H), 8.76 (s,5-H).

e)7-Methoxy-2-(5'-t-butyldimethylsilyl-2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

From the slower sub-zone (see 13 d), one obtains 168 mg (7.7%) ofproduct as colourless oil. TLC (silica gel, dichloromethane:acetone,95:5) Rf=0.55.

¹ H-NMR ([D₆ ]DMSO): δ=-0.163 and 0.111 (2 s, 2 SiCH₃), 0.72 (s,SiC(CH₃)₃), 2.17 (m, 3'-H), 2.65 and 2.56 (m, 2'-H), 3.66 (m, 5'-H),4.31 (m, 1'-H), 6.59 (d, J=5.6 Hz, 1'-H), 8.75 (s, 5-H).

f)7-Methoxy-1-(5"-t-butyldimethylsilyl-2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

Fraction II (see 13a, elution agent petroleum ether:ethyl acetate, 6:4)gives 118 mg (5.4%) of product as colourless oil. TLC (silica gel,petroleum ether:ethyl acetate, 6:4) Rf=0.5.

¹ H-NMR ([D₆ ]DMSO): δ=0.048 and 0.063 (2 s, 2 SiCH₃),0.87 (s,SiC(CH₃)₃), 1.98 (m, 3'-H), 2.75 and 2.60 (m, 2'-H), 3.66 (m, 5'-H),4.20 (s, OCH₃), 4.33 (m, 4'-H), 6.77 (dd, J=6.9 Hz and 2.9 Hz, 1'-H),8.8 (s, 5-H).

g)7-Methoxy-1-(5'-t-butyldimethylsilyl-2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

Fraction III (see 13a, elution agent petroleum ether:ethyl acetate, 6:4)gives 175 mg (8.0%) of product as colourless oil. TLC (silica gel,petroleum ether:ethyl acetate, 6:4) Rf=0.35.

¹ H-NMR ([D₆ ]DMSO): δ=-0.24 and -0.20 (2 s,2 SiCH₃), 0.67 (s,SiC(CH₃)₃), 2.15 (m, 3'-H), 2.87 and 2.60 (m, 2'-H), 3.40 (dd, J=11.1 Hzand 3.9 Hz, 5'-H), 4.28 (m, 4'-H), 6.68 (d, J=6.9 Hz, 1'-H), 8.75 (s,5-H).

h)7-Methoxy-3-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

500 mg (2.0 mmol) of the compound prepared according to 13b aredissolved in 20 ml THF, mixed with 2 ml of a 1.1N solution of Bu₄ NF inTHF andstirred for 2 h at RT. The solvent is evaporated off and thesyrupy residuechromatographed on silica gel 60 (column 20×3 cm,dichloromethane:methanol, 9:1). From the main fraction, one obtains 213mg(62%) of colourless, amorphous product. TLC (silica gel,dichloromethane:methanol 9:1) Rf=0.55.

¹ H-NMR ([D₆ ]DMSO): δ=1.97 (m, 3'-H), 2.63 (m, 2'-H), 3.47(m, 5'-H),4.21 (s, OCH₃), 4.36 (m, 4'-H), 4.81 (t, J=5.7 Hz, 5'-OH), 6.74 (dd,J=7.0 Hz and 3.4 Hz, 1'-H), 8.75 (s, 5-H).

i) 7-Methoxy-3-(2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

The protection removal of the compound prepared in 13c is carried out asdescribed for Example 13h. After 1 h, it is evaporated to dryness andchromatographed on silica gel (column 20×3 cm, dichloromethane:methanol95:5). From the main fraction, one obtains 291 mg(85%) of product ascolourless crystals. TLC (silica gel, dichloromethane:methanol, 9:1)Rf=0.65.

¹ H-NMR ([D₆ ]DMSO): δ=2.24 (m, 3'-H), 2.63 and 2.74 (m, 2'-H), 3.42 (m,5'-H), 4.22 (m, 4'-H and OCH₃), 4.70 (t, J=5.7 Hz, 5'-OH), 6.66 (dd,J=7.2 Hz and 2.2 Hz, 1'-H), 8.80 (s, 5-H).

7-Methoxy-2-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

500 mg (2.0 mmol) of the compound prepared according to 13d are treatedas described in Example 13h. After a reaction time of 1.25 h, thesolvent evaporated off and the oily residue chromatographed on silicagel 60 (column 20×3 cm, dichloromethane: methanol, 95:5). Evaporation ofthe main zone gives the product as crystalline compound. TLC (silicagel, dichloromethane:methanol, 9:1) Rf=0.45.

¹ H-NMR ([D₆ ]DMSO): δ=1.94 and 2.34 (2 m, 3'-H), 2.56 (m, 2'-H), 3.48(m, 5'-H), 4.18 (s, OCH₃), 4.46 (m, 4'-H), 4.85 (t, J=5.8Hz, 5'-OH),6.67 (dd, J=6.2 Hz and 2.5 Hz, 1'-H), 8.76 (s, 5-H).

k) 7-Methoxy-2-(2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

500 mg (2.0 mmol) of the compound prepared according to 13e are treatedas described in Example 13h. After a reaction time of 1 h, it isevaporated to dryness and chromatographed on silica gel 60 (column: 20×3cm, dichloromethane:methanol, 9:1). One thus obtains 286 mg (84%) ofamorphousproduct. TLC (silica gel, dichloromethane:methanol, 9:1)Rf=0.7.

¹ H-NMR ([D₆ ]DMSO): δ=2.17 (2m, 3'-H), 2.57 (m, 2'-H), 3.50 (m, 5'-H),4.16 (s, OCH₃), 4.28 (m, 4'-H), 4.76 (t, J=5.6 Hz, 5'-OH), 6.60 (dd,J=4.8 Hz and 3.2 Hz, 1'-H), 8.75 (s, 5-H).

7-Methoxy-l-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

500 mg (2.0 mmol) of the compound prepared according to 13f are treatedas described in Example 3h. After a reaction time of 1 h, it isevaporated todryness and chromatographed on silica gel 60 (column: 20×3cm, dichloromethane:methanol, 9;1). From the main fraction, one obtains246 mg(72%) of product. TLC (silica gel, dichloromethane:methanol, 9:1)Rf=0.6.

¹ H-NMR ([D₆ ]DMSO): δ=1.97 (m, 3'-H), 2.71 and 2.60 (m, 2'-H9, 3.47 (m,5'-H), 4.21 (s, OCH₃), 4.29 (m, 4'-H), 4.81 (t, J=5.7Hz, 5'-OH), 6.79(dd, J=7.4 Hz and 3.3 Hz, 1'-H ) , 8.75 (s, 5-H ).

m)7-Methoxy-1-'2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

500 mg (2.0 mmol) of the compound prepared according to 13g are treatedas described in Example 3h. After a reaction time of 0.5 h, it isevaporated to dryness and chromatographed on silica gel 60 (column: 20×3cm, dichloromethane:methanol, 9:1). One thus obtains 303 mg (89%) ofproduct. TLC (silica gel, dichloromethane:methanol, 9:1) Rf=0.5.

¹ H-NMR ([D₆ ]DMSO): δ=2.19 (m, 3'-H), 2.60 and 2.79 (2 m, 2'-H), 3.33(m, 5'-H), 4.20 (s, OCH₃), 4.23 (m, 4'-H), 4.64 (t, J=5.6Hz, 5'-OH),6.69 (d, J=5.7 Hz, 1'-H), 8.75 (s, 5-H).

EXAMPLE 147-Amino-3-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg (0.4 mmol) of the compound prepared according to 13h are stirredfor24 h at RT in 10 ml of methanolic NH₃ (saturated at 0° C). After thesolvent has been evaporated off, the crude product is purified bychromatography (silica gel 60, column: 10×2 cm,dichloromethane:methanol, 9:1). From the main fraction, one obtains 69mg (74%) of product as crystalline solid. TLC (silica gel,dichloromethane:methanol, 9:1) Rf=0.3.

¹ H-NMR ([D₆ ]DMSO): δ=1.91 and 2.36 (2 m, 3'-H), 2.7-2.5 (2'-H), 3.46(m, 5'-H), 4.33 (m, 4'-H), 4.80 (t, J=5.7 Hz, 5'-OH), 6.61 (dd, J=7.0and 3.5 Hz, 1'-H), 8.12 and 8.45 (2s, 2NH), 8.32 (s, 5-H).

EXAMPLE 157-Amino-3-(2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg (0.4 mmol) of the compound prepared according to 13i are treatedas described in Example 14. After the solvent has been evaporated off,the crude product is purified by chromatography (silica gel 60, column:10×2 cm, dichloromethane: methanol, 9:1). After evaporation of the mainfraction, one obtains 83 mg (87%) of product which crystallises frommethanol in colourless needles of the m.p. 182° C. TLC (silicagel,dichloromethane:methanol, 9:1) Rf=0.54.

¹ H-NMR ([D₆ ]DMSO): δ=2.24 (m, 3'-H), 2.59 and 2.70 (2 m, 2'-H), 3.46(m, 5'-H), 4.81 (t, J=5.7 Hz, 5'-OH), 6.55 (dd, J=7.1 and 2.7 Hz, 1-H),8.47 and 8.14 (2s, 2 NH), 8.33 (s, 5-H).

EXAMPLE 167-Amino-2-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg of the compound prepared according to 13j are treated asdescribed in Example 14. The reaction takes 7 h. After evaporation ofthe solvent and chromatography on silica gel (column 10×2 cm,dichloromethane:methanol, 9:1), one obtains crystalline product. TLC(silica gel, dichloromethane:methanol, 9:1) Rf=0.5.

¹ H-NMR ([D₆ ]DMSO): δ=1.94 and 2.35 (2 m, 3'-H), 2.55 (m, 2'-H), 3.49(m, 5'-H), 4.43 (m, 4'-H), 4.85 (t, J=5.3 Hz, 5'-OH), 6.56 (pt, J=4.5Hz, 1'-H), 8.1 (s, NH₂), 8.32 (s, 5-H).

EXAMPLE 177-Amino-2-(2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg of the compound prepared according to 13k are treated asdescribed in Example 14. After 8 h, it is evaporated to dryness andchromatographed on silica gel (column 10×2 cm, dichloromethane:methanol,9:1). TLC (silica gel, dichloromethane:methanol, 9:1) Rf=0.35.

¹ H-NMR ([D₆ ]DMSO): δ=2.17 (m, 3'-H), 2.54 (m, 2'-H), 3.48(pt, J=5.6Hz, 5'-H), 4.24 (m, 4'-H), 4.75 (t, J=5.6 Hz, 5'-OH), 6.47 (d, J=4.4 Hz,1'-H), 8.10 (s, NH), 8.32 (s, NH and 5-H).

EXAMPLE 187-Amino-1-(2',3'-didesoxy-α-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg of the compound prepared according to 13l are treated asdescribed in Example 14. After 36 h, the solvent is evaporated off andthe crude product purified by chromatography (silica gel 60, column:10×2 cm, dichloromethane:methanol, 9:1). After evaporation of the mainfraction, one obtains 63 mg (67%) of product which crystallises fromacetone in fineneedles. TLC (silica gel, dichloromethane :methanol, 9:1)Rf=0.25.

¹ H-NMR ([D₆ ]DMSO): δ=1.93 and 2.15 (2 m, 3'-H), 3.51 (m, 5'-H), 4.17(m, 4'-H), 4.91 (t, J=5.7 Hz, 5'-OH), 6.76 (dd, J=6.3 Hz and 1.7 Hz,1'-H), 7.78 (s, NH₂), 8.35 (s, 5-H).

EXAMPLE 197-Amino-1-(2',3'-didesoxy-β-D-erythro-pentofuranosyl)-3H-1,2,3-triazolo[4,5-d]pyrimidine.

100 mg of the compound prepared according to 13m are treated asdescribed in Example 14. After 36 h, it is evaporated to dryness andchromatographedon silica gel (column: 10×2 cm, dichloromethane:methanol,9:1). From the main zone, there are obtained 58 mg (62%) of crystallineproduct. TLC (silica gel, dichloromethane:methanol, 9:1) Rf=0.25.

1H-NMR ([D₆ ]DMSO): δ=1.93 and 2.16 (2 m, 3'-H), 2.49 (m, 2'-H),3.15 (m,5'-H), 4.36 (m, 4'-H), 4.77 (t, J=5.2 Hz, 5'-OH), 6.64 (dd, J=4.5 Hz,1'-H), 7.76 (s, NH₂), 8.33 (s, 5-H).

EXAMPLE 204-Amino-1-(2,3-didesoxy-α(β)-D-glyceropentofuranosyl)-1H-imidazo[4,5-c]pyridine.

a)4-Chloro-1-(5-O-[(1,1-dimethylethyl)-dimethylsilyl]-2,3-dideoxy-α(.beta.)-D-glyceropentofuranosyl)-1H-4,5-c]pyridine.

4 Chloroimidazo[4,5-c]pyridine (809 mg, 5.3 mmol) is reacted asdescribed in Example 12a with5-O-[(1,1-dimethylethyl)-dimethylsilyl]-2,3-dideoxy-D-glyceropentofuranosylchloride (prepared from 2.6 g, 11 mmol of the lactol) and worked up.[TLC(silica gel, CH₂ Cl₂ -MeOH 95:5): Rf=0.77]. The anomericmixture,obtained as colourless oil, is dissolved in EtOAc-petroleumether 3:7 and chromatographed on silica gel 60 H (column: 35×6 cm, 0.8bar, EtOAc-petroleum ether, 3:7). From the more quickly moving zone, oneobtains, after evaporation, 390 mg (23%) of the α-anomer as colourlesscrystals of the m.p. 65°-68° C. (EtOAc).

¹ H-NMR ([D₆ ]DMSO): δ=8.63 (s, H-1), 8.18 (d, J=5.6 Hz, H-6), 7.73 (d,J=5.6 Hz, H-7), 6.39 (dd, J=6.4, 4.0 Hz, H-1'), 4.39 (m, H-4'), 3.65 (m,H₂ -5'), 2.4 (m, H₂ -2'), 2.20 (m, H.sub.α-3'), 1.94 (m, H.sub.β -3'),0.87 (s, t-Bu-Me), 0.06 (s, Si-Me).

From the more slowly moving zone, after evaporation, one obtains 420 mg(25%) of the β-anomer as colourless foam.

¹ N-NMR ([D₆ ]DMSO): δ=8.65 (s, H-2), 8.14 (d, J=5.6 Hz, H-6), 7.75 (d,J=5.6 Hz, H-7), 6.31 (pt, J=4.3 Hz, H-1'), 4.20 (m, H-4'), 3.69 (m, H₂-5'), 2.5 (m, H₂ -2'), 2.04 (m, H₂ -3'), 0.78 (s, t-Bu-Me), 0.05-0.07(s, Si-Me).

b)4-Chloro-1-(2,3-dideoxy-β-D-glyceropentofuranosyl)-1H-imidazo[4,5-c]pyridine.

The β-anomer obtained in Example 20a (300 mg, 0.9 mmol) is dissolved inTHF (5 ml) and mixed with Bu₄ NF (1M in THF, 5 ml) and stirred for15 minat RT. One evaporates to a colourless oil and chromatographs on silicagel 60H (column 10×6 cm, 0.5 bar, CH₂ Cl₂ -MeOH 9:1). After evaporationof the main zone, one obtains 170 mg (86%) of product as colourless oil.TLC (silica gel, CH₂ Cl₂ -MeOH 9:1) RF=0.45.

¹ H-NMR ([D₆ ]DMSO): δ=8.73 (s, H-2), 8.15 (d, J=5.6 Hz, H-6), 7.78 (d,J=5.6 Hz, H-7), 6.32 (dd, J=6.4 Hz, 3.4 Hz, H-1'), 4.98 (t,J=5.3 Hz,5'-OH), 4.13 (m, H-4'), 3.53 (m, H₂ -5'), 2.4 (m, H₂ -2'), 2.05 (m, H₂-3').

c)4-Chloro-1-(2,3-dideoxy-α-D-glyceropentofuranosyl)-1H-imidazo[4,5-c]pyridine.

The α-anomer obtained in Example 20a (300 mg, 0.9 mmol) is reactedasdescribed in Example 12b and worked up. One obtains 160 mg (81%) ofcolourless crystals. TLC (silica gel, CH₂ Cl₂ -MeOH 9:1) Rf=0.42.

¹ H-NMR ([D₆ ]DMSO): δ=8.64 (s, H-2), 8.17 (d, J=5.6 Hz, H-6), 7.74 (d,J=5.6 Hz, H-7), 6.39 (dd, J=6.2 Hz, 4.1Hz, H-1'), 4.86 (t, J=5.3 Hz,5'-OH), 4.34 (m, H-4'), 3.46 (m, H₂ -5'), 2.5 (m, H₂ -2'), 2.19 and 1.93(2m, H₂ -3').

d)4-Amino-1-(2,3-dideoxy-β-D-glyceropentofuranosyl)-1H-imidazo[4,5-c]pyridine.

The product obtained in Example 20b (100 mg, 0.46 mmol) is mixed withhydrazine hydrate (100%, 10 ml) and stirred for 90 min at 90°-100° C.under N₂. After evaporation of excess hydrazine hydrate, it isrepeatedly evaporated with EtOH and the residue dissolved in EtOH (25ml). One adds 2 g of Raney nickel thereto and boils under reflux for 2h. After filtering off of the catalyst, the filtrate isevaporated andthe residue chromatographed on silica gel 60H (column: 6×6 cm, 0.5 bar,CH₂ Cl₂ -MeOH 9:1). After evaporation of the main zone, one obtains 40mg (37%) of the title compound as colourlessfoam. TLC (silica gel, CH₂Cl₂ -MeOH 9:1) Rf=0.4.

¹ H-NMR ([D₆ ]DMSO): δ=8.33 (s, H-2), 7.67 (d, J=5.8 Hz, H-6), 6.65 (d,J=5.8 Hz, H-7), 6.25 (s, br., NH₂), 6.14 (dd, J=6.5 Hz, 3.8 Hz, H-1'),4.12 (m, H-4'), 3.53 (m, H₂ -5'), 2.33 (m, H₂-2'), 2.01 (2 m, H₂ -3').

EXAMPLE 211-(2,3-Didesoxy-β-D-glyceropentofuranosyl)-imidazo[1,2-a]pyrimidin-2-one.

a)7-Chloro-1-(2,3-didesoxy-5-O-(tert.-butyldimethsilyl)-β-D-glyceropentofuranosyl)-imidazo[1,2-a]-pyrimidin-5-oneand its α-anomer

1.0 g (5.9 mmol) 7-chloroimidazo[1,2-a]-pyrimidin-5-one (R. G. Revankaret al., Anm. N.Y. Acad. Sci., 255, 166, 1975) is dissolved in a mixtureof 10ml DMF and 50 ml THF and stirred with 3.0 g KOH and 30 μl TDA-1 for30 min at room temperature. 5-O-[(1,1-Dimethylethyl)dimethylsilyl]-2,3-didesoxy-D-glyceropentofuranosyl chloride (13 mmol) prepared insitu according to Example 4a, are injected therein in 4 portions. Onefurther stirs for 45 min at room temperature, filters, adds 300 ml ofsaturated NaHCO₃ solution thereto and extracts the aqueous phase withCHCl₃. The organic extract is dried with Na₂ SO₄ and evaporated in avacuum. Chromatography on silica gel 60 gives 450 mg (20%)of theα-anomer (rapid zone) as colourless oil and 590 mg (26%) of the β-anomer(slow zone) as colourless crystals of the m.p. 63° C. (ether).

(β-anomer): ¹ H-NMR ([D₆ ]DMSO): δ=0.06 (s, 6H, CH₃), 0.87 (s, 9H, CH₃),1.68 (m, 2H, H-3'), 2.25 (m, 2H, H-2'),3.62 (m, 2H, H-5'), 4.45 (m, 1H,H-4'), 5.99 (s, 1H, H-6), 6.27 (dd, J=3.9 Hz, J=6.8 Hz, 1H, H-1'), 7.73(d, J=2.7 Hz, 1H, H-3), 7.80 (d, J=2.7 Hz, 1H, H-2). (α-anomer): δ=0.02(s, 6H, CH₃), 0.64 (s, 9HM CH₃), 2.02 (m, 2H, H-3'), 2.38 (m, 2H, H-2'),3.76 (m, 2H, H-5'), 4.14 (m, 1H, H-4'), 5.99 (s, 1H, H-6), 6.21 (m, 1H,H-1'), 7.72 (d, J=2.4Hz, 1H, H-3), 7.79 (d, J=2.4 Hz, 1H, H-2).

b)7-Chloro-1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-imidazo[1,2-a]pyrimidin-5-one

250 mg (0.65 mmol) of the β-anomer prepared according to a) aredissolved in THF, mixed with 2 ml Bu₄ NF (1M solution in THF) andstirred for 60 min at room temperature. After the evaporation off of thesolvent, one chromatographs on a 20×2 cm silica gel 60 column. The mainzone gives the product as colourless crystals (74%) of the m.p. 157° C.(propanol-2).

¹ H-NMR ([D₆ ]DMSO): δ=2.00 (m, 2H, H-3'), 2.37 (m, 2H, H-2'), 3.60 (m,2H,H-5'), 4.10 (m, 1H, H-4'), 5.01 (t, J=5.4 Hz, 1H, OH), 5.99 (s, 1H,H-6), 6.22 (dd, J=217 Hz, J=6.7 Hz, 1H, H-1'), 7.73 (d, J=2.6Hz, 1H,H-3), 7.92 (d, J=2.6 Hz, 1H, H-2).

c)1-(2,3-Didesoxy-β-D-glycerqpentofuranosyl)imidazo[1,2-a]pyrimidin-5-one

60 mg (0.22 mmol) of the compound prepared according to b) are dissolvedin50 ml ethanol. One adds 4 ml conc. NH₃ thereto and hydrogenates with100 mg of Pd (10% Pd on C) for 14 h at RT. The catalyst is filtered off,washed with hot ethanol and the filtrate evaporated. Flashchromatography on silica gel 60 gives 12 mg (23%) of product.

¹ H-NMR ([D₆ ]DMSO): δ=2.00 (m, 2H, H-3'), 2.30 (m, 2H, H-2'), 3.60 (m,2H, H-5'), 4.10 (m, 1H, H-4'), 5.03 (t, J=5.4 Hz, 1H, OH),5.90 (d, J=6.3Hz, 1H, H-6), 6.28 (dd, J=3.2 Hz, J=6.8 Hz, 1H, H-1'), 7.68 (d, J=2.7Hz, 1H, H-3), 7.86 (d, J=2.7 Hz, 1H, H-2), 7.94 (d, J=6.3 Hz, 1H, H-7).

EXAMPLE 227-Amino-1-(2,3-didesoxy-β-D-glyceropentofuranosyl)imidazo[1,2-a]pyrimidin-5-one.

One obtains the title compound from 60 mg (0.22 mmol) of the compoundprepared according to Example 21b) analogously to the procedure for thecorresponding ribo compound (R. G. Revanker et al., Anm. New York Sci.,255, 166, 1975). TLC (silica gel, dichloromethane:methanol, 9:1)Rf=0.35.

We claim:
 1. Nucleoside derivatives of formula I ##STR6## wherein Ba isan indolyl (A), benzimidazolyl (B), pyrrolopyridinyl (C),imidazopyridinyl (D), triazolopyrimidinyl (E), imidazotriazinyl (F) orimidazopyrimidinyl (G) group, of the following formulae, respectively:##STR7## wherein R¹, R², R³, which can be the same or different, arehydrogen, halogen, C₁ -C₇ -alkyl, C₂ -C₇ -alkenyl, hydroxy, mercapto, C₁-C₇ -alkylthio, C₁ -C₇ -alkoxy, C₂ -C₇ -alkenyloxy, aryl-C₁ -C₅ -alkyl,aryl-C₂ -C₅ -alkenyl, aryl-C₁ -C₅ -alkoxy, aryl-C₂ -C₅ -alkenyloxy,aryloxy, nitro, amino-C₁ -C₇ -alkyl, C₁ -C₇ -alkylamino-C₁ -C₇ -alkyl,di-C₁ -C₇ -alkylamino-C₁ -C₇ -alkyl, amino, substituted amino group ofthe formula --NHR⁴ or --N(R⁴)₂ or an imino group --N═CH--R⁴, wherein R⁴is C₁ -C₇ -alkyl, C₂ -C₇ -alkenyl, C₃ -C₇ -cycloalkyl, C₃ -C₇-cycloalkyl-C₁ -C₇ -alkyl, C₃ -C₇ -cycloalkenyl, C₁ -C₇ -alkoxy-C₁ -C₇-alkyl, halogen-C₁ -C₇ -alkyl, hydroxy-C₁ -C₇ -alkyl, aryl-C.sub. 1 -C₅-alkyl, aryl-C₂ -C₅ -alkenyl, hetaryl-C₁ -C₅ -alkyl or hetaryl-C₂ -C₅-alkenyl radical, wherein the aryl and hetaryl moieties areunsubstituted or are substituted one, two or three times by C₁ -C₆-alkyl, C₂ -C₆ -alkenyl, C₁ -C₆ -alkoxy, halogen or hydroxyl, or R⁴ isamino-C₁ -C₇ -alkyl, C₁ -C₇ -alkylamino-C₁ -C₇ -alkyl or di-C₁ -C₇-alkylamino-C₁ -C₇ -alkyl and, in the case of the --NHR⁴ and --N═CH--R⁴groups, R⁴ can additionally be amino, C₁ -C₇ -alkylamino, di-C₁ -C₇-alkylamino or C₁ -C₇ -alkoxy or, in the case of the --N(R⁴)2 group, thetwo nitrogen substituents R⁴ together can form a C₁ -C₇ -alkylidenegroup which, in turn, can be unsubstituted or substituted by C₁ -C₇-alkoxy, C₁ -C₇ -alkylamino or di-C₁ -C₇ -alkylamino, wherein said arylis phenyl or naphthyl and said hetaryl is furanyl, thienyl or pyridyl,R⁵, R⁶, R⁷, and R⁸ each are hydrogen, or one or two of R⁵, R⁶, R⁷, andR⁸ are hydroxyl, halogen, cyano, azido or a substituted amino group--NHR⁴ or --N(R⁴)₂, or and R⁵ and R⁷ can together represent a furtherbond between C-2' and C-3', and Y is hydrogen or C₁ -C₇ -alkylcarbonyl,monophosphate, diphosphate or triphosphate,with the provisos that a)when R⁶ is a hydroxyl group, R⁸ is other than a hydrogen atom or ahydroxyl group, b) when Ba is the group (B) , R⁶ is other than ahalogen, amino or azido group, c) when Ba is the group (D) and R² ishydrogen, R¹ is other than chlorine or amino and R⁶ is other thanhydrogen or chlorine, and d) When Ba is the group (E) and R¹ is amino,R⁵ and R⁷ cannot together represent a bond,as well as their possible αand β-anomers, , N⁷ -, N⁸ - or N⁹ regioisomers (purine nomenclature),tautomers and salts, and nucleic acids which contain compounds of theformula I as constructional units.
 2. Nucleoside of claim 1, wherein R¹is hydrogen, amino, C₁ -C₆ -alkoxy, halogen or nitro, R² is hydrogen,halogen or amino, R³ is hydrogen and R⁵ -R⁸ are hydrogen atoms, or R⁶and R⁸ are hydrogen and R⁵ and R⁷ together form a bond.
 3. Nucleoside ofclaim 1, wherein Ba is group (A), R¹ is amino or nitro and R² R³, and R⁵-R⁸ are each hydrogen or R², R³, R⁶ and R⁸ are hydrogen and R⁵ and R⁷together form a bond.
 4. Nucleoside of claim 1, wherein Ba is group (B)and R¹, R² and R⁵ -R⁸ are each hydrogen.
 5. Nucleoside of claim 1,wherein Ba is group (C), R¹ is hydrogen, amino or nitro, and R², R³, R⁵-R⁸ each are hydrogen, or R², R³, R⁶ and R⁸ are hydrogen and R⁵ and R⁷together form a bond.
 6. Nucleoside of claim 1, wherein Ba is group (D)and R¹ is amino or chlorine, and R² and R⁵ -R⁸ each are hydrogen. 7.Nucleoside of claim 1, wherein Ba is group (E), R¹ is amino or C₁ -C₆-alkoxy and R² and R⁵ -R⁸ each are hydrogen.
 8. Nucleoside of claim 1,wherein Ba is group (F) , R² is hydrogen or amino and R³ and R⁵ -R⁸ areeach hydrogen.
 9. Nucleoside of claim 1, wherein Ba is group (G) , R² ishydrogen, amino or chlorine and R³ and R⁵ -R⁸ are each hydrogen. 10.Nucleotide of claim 1, wherein said nucleotide is1-(2,3-didesoxy-β-D-glyceropentofuranosyl)-1 H-pyrrolo-[2,3-b]pyridine5¹ -triphosphate or1-(2,3-didesoxy-β-D-glyceropent-2-enofuranosyl)-4-nitro-1H-pyrrolo[2,3-b]pyridine5¹ -triphosphate.
 11. Nucleotide of claim 10, wherein said nucleotide isin the form of the triethylammonium salt.
 12. Nucleoside derivative offormula I ##STR8## wherein Ba is an indolyl, pyrrolopyridinyl,imidazopyridinyl, imidazotriazinyl or imidazopyrimidinyl group;R¹ ishydrogen, amino, C1-C6-alkoxy, halogen or nitro; R² is hydrogen, halogenor amino; R³ is hydrogen; R⁵ is hydrogen; R⁶ is hydrogen, halogen, cyanoor azido; R⁷ is hydrogen; and R⁸ is hydrogen or R⁵ and R⁷ together forma bond; with the proviso that when Ba is the group (E) and R¹ is amino,R⁵ and R⁷ cannot together represent a bond,as well as their possible αand β-anomers, N⁷ -, N⁸ - or N⁹ regioisomers (purine nomenclature),tautomers and salts, and nucleic acids which contain compounds of theformula I as constructional units.